[Sitemap] [Kontakt] [Impressum] Inhalt in Englisch Suchen 

Amino Acids - Aktuelle Forschungsartikel



Aktuelle Forschungsartikel: Aminosäuren

Die Urheberrechte und Veröffentlichungsrechte der in der nachfolgenden Liste aufgeführten Fachartikel liegen bei den jeweiligen Verlagen, die am Ende des jeweiligen Artikels als Quelle genannt werden. Diese sind auch für die Inhalte verantwortlich.

Weitere aktuelle Fachartikel von Chemiezeitschriften ähnlicher Thematik finden Sie im Navigationsmenue links.

Hinweise zur Veröffentlichung Ihrer Pressemitteilung unter Internetchemie.Info entnehmen Sie bitte der entsprechenden Info-Seite.

Diese Seite können Sie mit folgender Tastenkombination nach Stichwörtern durchsuchen: <STRG> und <F>.




Hier aufgeführte Forschungsartikel:



Amino Acids - Verlag: Springer

Die wissenschaftliche Zeitschrift 'Amino Acids' veroeffentlicht Beitraege aus allen Bereichen der Aminosaeure- und Protein-Forschung: Analyse-Methoden, Trennungs-Methoden, Synthese, Biosynthese, Vernetzung von Aminosaeuren, Racemisierung/Enantiomerie, Modifikation von Aminosaeuren durch Phosphorylierung, Methylierung, Acetylierung, Glykosylierung und nichtenzymatische Glykosylierung, neue Rollen fuer Aminosaeuren in der Physiologie und Pathophysiologie, Biologie; Aminosaeure-Analoga und Derivate, Polyamine, bestrahlte Aminosaeuren, Peptide, Isotope der Aminosaeuren. Anwendungen in Medizin, Lebensmittelchemie, Ernaehrung, Gastroenterologie, Nephrologie, Neurochemie, Pharmakologie, etc sind nur einige der behandelten Themen.




Wissenschaftliche Fachartikel:



Metal ion dependency of serine racemase from Dictyostelium discoideum

Abstract  
d-Serine is known to act as an endogenous co-agonist of the N-methyl-d-aspartate receptor in the mammalian brain and is endogenously synthesized from l-serine by a pyridoxal 5?-phosphate-dependent enzyme, serine racemase. Though the soil-living mycetozoa Dictyostelium discoideum possesses no genes homologous to that of NMDA receptor, it contains genes encoding putative proteins relating to the d-serine metabolism, such as serine racemase, d-amino acid oxidase, and d-serine dehydratase. D. discoideum is an attractive target for the elucidation of the unknown functions of d-serine such as a role in cell development. As part of the elucidation of the role of d-serine in D. discoideum, we cloned, overexpressed, and examined the properties of the putative serine racemase exhibiting 46% amino acid sequence similarity with the human enzyme. The enzyme is unique in its stimulation by monovalent cations such as Na+ in addition to Mg2+ and Ca2+, which are well-known activators for the mammalian serine racemase. Mg2+ or Na+ binding caused two- to ninefold enhancement of the rates of both racemization and dehydration. The half-maximal activation concentrations of Mg2+ and Na+ were determined to be 1.2 ?M and 2.2 mM, respectively. In the l-serine dehydrase reaction, Mg2+ and Na+ enhanced the k cat value without changing the K m value. Alanine mutation of the residues E207 and D213, which correspond to the Mg2+-binding site of Schizosaccharomyces pombe serine racemase, abolished the Mg2+- and Na+-dependent stimulation. These results suggest that Mg2+ and Na+ share the common metal ion-binding site.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-10
  • DOI 10.1007/s00726-012-1232-z
  • Authors
    • Tomokazu Ito, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan
    • Hirotaka Murase, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan
    • Motoki Maekawa, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan
    • Masaru Goto, Department of Biomolecular Science, Faculty of Science, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan
    • Shuhei Hayashi, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan
    • Hajime Saito, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan
    • Masatoshi Maki, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan
    • Hisashi Hemmi, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan
    • Tohru Yoshimura, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 6 February 2012 | 8:33 pm


Interactions of acidic pharmaceuticals with human serum albumin: insights into the molecular toxicity of emerging pollutants

Abstract  
Acidic pharmaceuticals such as diclofenac (DCF), clofibric acid (CA) and ketoprofen (KTP) have been detected frequently in environmental media. In order to reveal the toxicity of such emerging pollutants, their interactions with human serum albumin (HSA) were investigated by capillary electrophoresis, molecular spectrometry, and equilibrium dialysis. The binding constants and sites of these acidic pharmaceuticals with HSA were obtained. The thermodynamic parameters, e.g. enthalpy change and entropy change of these interactions were calculated to characterize that all the reactions resulted from hydrophobic and electrostatic interactions. The static quenching of the fluorescence of HSA was observed when interacted with acidic pharmaceuticals, indicating acidic pharmaceuticals bound to Tryptophan residue of HSA. The 3D fluorescence and circular dichroism confirmed that the secondary conformation of HSA changed after the interactions with the pharmaceuticals. At physiological condition, only 0.12 mM acidic pharmaceuticals reduced the binding of vitamin B2 to HSA by 37, 30 and 21% for DCF, KTP and CA, respectively. This work provides an insight into non-covalent interactions between emerging contaminants and biomolecule, and is helpful for clarifying the toxic mechanism of such emerging contaminants.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-11
  • DOI 10.1007/s00726-012-1215-0
  • Authors
    • Jiabin Chen, Key Laboratory of Yangtze River Water Environment for Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092 China
    • Xuefei Zhou, Key Laboratory of Yangtze River Water Environment for Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092 China
    • Yalei Zhang, Key Laboratory of Yangtze River Water Environment for Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092 China
    • Yajie Qian, Key Laboratory of Yangtze River Water Environment for Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092 China
    • Haiping Gao, Key Laboratory of Yangtze River Water Environment for Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092 China
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 3 February 2012 | 6:12 pm


Transglutaminases: key regulators of cancer metastasis

Abstract  
The ability to metastasize represents the most important characteristic of malignant tumors. The biological details of the metastatic process remain somewhat unknown, due to difficulties in studying tumor cell behaviour with high spatial and temporal resolution in vivo. Several lines of evidence involve transglutaminases (TGs) in the key stages of tumor progression cascade, even though the molecular mechanisms remain controversial. TG expression and activity display a different role in the primary tumor or in metastatic cells. In fact, TG expression is low in the primary tumor mass, but augmented when cells acquire the metastatic phenotype. Nevertheless, in other cases, the use of inducers of TG transamidating activity seems to contrast tumor cell plasticity, migration and invasion. In the following review, the function of TGs in cancer cell migration into the extracellular matrix, adhesion to the capillary endothelium and its basement membrane, invasion and angiogenesis is discussed.

  • Content Type Journal Article
  • Category Invited Review
  • Pages 1-8
  • DOI 10.1007/s00726-012-1229-7
  • Authors
    • Alessandro Lentini, Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00133 Rome, Italy
    • Alberto Abbruzzese, Department of Biochemistry and Biophysics, Second University of Naples, Naples, Italy
    • Bruno Provenzano, Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00133 Rome, Italy
    • Claudio Tabolacci, Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00133 Rome, Italy
    • Simone Beninati, Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00133 Rome, Italy
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 2 February 2012 | 6:57 pm


Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stress-related signaling pathways and apoptosis in rats

Abstract  
Hyperglycemia-induced oxidative stress plays a vital role in the progression of diabetic nephropathy. The renoprotective nature of taurine has also been reported earlier; but little is known about the mechanism of this beneficial action. The present study has, therefore, been carried out to explore in detail the mechanism of the renoprotective effect of taurine under diabetic conditions. Diabetes was induced in rats by alloxan (single i.p. dose of 120 mg/kg body weight) administration. Taurine was administered orally for 3 weeks (1% w/v in drinking water) either from the day on which alloxan was injected or after the onset of diabetes. Alloxan-induced diabetic rats showed a significant increase in plasma glucose, enhanced the levels of renal damage markers, plasma creatinine, urea nitrogen and urinary albumin. Diabetic renal injury was associated with increased kidney weight to body weight ratio and glomerular hypertrophy. Moreover, it increased the productions of reactive oxygen species, enhanced lipid peroxidation and protein carbonylation in association with decreased intracellular antioxidant defense in the kidney tissue. In addition, hyperglycemia enhanced the levels of proinflammatory cytokins (TNF-?, IL-6, IL-1?) and Na+–K+-ATPase activity with a concomitant reduction in NO content and eNOS expression in diabetic kidney. Investigation of the oxidative stress-responsive signaling cascades showed the upregulation of PKC?, PKC?, PKC? and MAPkinases in the renal tissue of the diabetic animals. However, taurine administration decreased the elevated blood glucose and proinflammatory cytokine levels, reduced renal oxidative stress (via decrease in xanthine oxidase activity, AGEs formation and inhibition of p47phox/CYP2E1 pathways), improved renal function and protected renal tissue from alloxan-induced apoptosis via the regulation of Bcl-2 family and caspase-9/3 proteins. Taurine supplementation in regular diet could, therefore, be beneficial to regulate diabetes-associated renal complications.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-15
  • DOI 10.1007/s00726-012-1225-y
  • Authors
    • Joydeep Das, Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata, 700054 India
    • Parames C. Sil, Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata, 700054 India
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 2 February 2012 | 6:57 pm


Site-selective radiolabeling of peptides by 18F-fluorobenzoylation with [18F]SFB in solution and on solid phase: a comparative study

Abstract  
Peptides labeled with short-lived positron-emitting radionuclides are of outstanding interest as probes for molecular imaging by positron emission tomography (PET). Herein, the site-selective incorporation of fluorine-18 into lysine-containing peptides using the prosthetic labeling agent N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) is described. The reaction of [18F]SFB with four biologically relevant resin-bound peptides was studied and optimized. For comparison, each peptide was 18F-fluorobenzoylated in solution under different conditions and the product distribution was analyzed confirming the advantages of the solid-phase approach. The method’s feasibility for selective radiolabeling either at the N-terminus or at the lysine side chain was demonstrated. Labeling on solid phase with [18F]SFB resulted in crude 18F-fluorobenzoylpeptides whose radiochemical purities were typically greater than 90% and that could be prepared in synthesis times from 65 to 76 min.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-13
  • DOI 10.1007/s00726-012-1216-z
  • Authors
    • Manuela Kuchar, Institut für Radiopharmazie, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany
    • Marc Pretze, Institut für Radiopharmazie, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany
    • Torsten Kniess, Institut für Radiopharmazie, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany
    • Jörg Steinbach, Institut für Radiopharmazie, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany
    • Jens Pietzsch, Institut für Radiopharmazie, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany
    • Reik Löser, Institut für Radiopharmazie, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 2 February 2012 | 6:57 pm


Antidepressant effect of taurine in diabetic rats

Abstract  
Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-9
  • DOI 10.1007/s00726-012-1226-x
  • Authors
    • Greice Caletti, Programa de Pós Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil
    • Danielly B. Olguins, Programa de Pós Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil
    • Elis F. Pedrollo, Departamento de Ciências da Saúde, Disciplina de Farmacologia, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil
    • Helena M. T. Barros, Programa de Pós Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil
    • Rosane Gomez, Programa de Pós Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 2 February 2012 | 6:57 pm


Non-canonical interactions of porphyrins in porphyrin-containing proteins

Abstract  
In this study we have described the non-canonical interactions between the porphyrin ring and the protein part of porphyrin-containing proteins to better understand their stabilizing role. The analysis reported in this study shows that the predominant type of non-canonical interactions at porphyrins are CH···O and CH···N interactions, with a small percentage of CH···? and non-canonical interactions involving sulfur atoms. The majority of non-canonical interactions are formed from side-chains of charged and polar amino acids, whereas backbone groups are not frequently involved. The main-chain non-canonical interactions might be slightly more linear than the side-chain interactions, and they have somewhat shorter median distances. The analysis, performed in this study, shows that about 44% of the total interactions in the dataset are involved in the formation of multiple (furcated) non-canonical interactions. The high number of porphyrin–water interactions show importance of the inclusion of solvent in protein–ligand interaction studies. Furthermore, in the present study we have observed that stabilization centers are composed predominantly from nonpolar amino acid residues. Amino acids deployed in the environment of porphyrin rings are deposited in helices and coils. The results from this study might be used for structure-based porphyrin protein prediction and as scaffolds for future porphyrin-containing protein design.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-12
  • DOI 10.1007/s00726-012-1228-8
  • Authors
    • Sr?an ?. Stojanovi?, Department of Chemistry, ICTM, University of Belgrade, Njegoševa 12, Belgrade, 11000 Serbia
    • Esma R. Isenovi?, Laboratory for Molecular Genetics and Radiobiology, Institute Vin?a, University of Belgrade, P.O. Box 522, 11001 Belgrade, Serbia
    • Božidarka L. Zari?, Department of Chemistry, ICTM, University of Belgrade, Njegoševa 12, Belgrade, 11000 Serbia
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 2 February 2012 | 6:57 pm


Induction of NAD(P)H:quinone oxidoreductase 1 expression by cysteine via Nrf2 activation in human intestinal epithelial LS180 cells

Abstract  
In this study, we examined the effects of 20 amino acids on the expression level of NAD(P)H:quinone oxidoreductase 1 (NQO1) in human intestinal LS180 cells. Five amino acids were associated with significant increases in NQO1 mRNA expression; the most substantial increase was induced by cysteine, which markedly increased the NQO1 mRNA level in a time- and dose-dependent manner. Cysteine also increased the protein level of NQO1 and its enzymatic activity in LS180 cells. Furthermore, cysteine significantly up-regulated NQO1 promoter activity, and this induction was completely abolished by mutation of the antioxidant response element, a binding site of the nuclear factor erythroid 2-related factor 2 (Nrf2). Knockdown experiment using siRNA against Nrf2 showed the involvement of Nrf2 on cysteine-induced increase in NQO1 mRNA expression. Further, cysteine treatment increased the amount of Nrf2 protein in the nucleus and decreased the amount of Kelch-like ECH-associated protein 1 (a suppressor protein of Nrf2) in the cytosol, suggesting that Nrf2 was activated by cysteine. Oral administration of cysteine to mice significantly increased NQO1 mRNA levels in the mouse intestinal mucosa. These findings show that cysteine induces NQO1 expression in both in vitro and in vivo systems and also suggest that Nrf2 activation is involved in this induction.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-9
  • DOI 10.1007/s00726-012-1230-1
  • Authors
    • Hideo Satsu, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657 Japan
    • Emi Chidachi, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657 Japan
    • Yuto Hiura, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657 Japan
    • Haru Ogiwara, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657 Japan
    • Yusuke Gondo, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657 Japan
    • Makoto Shimizu, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657 Japan
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 2 February 2012 | 6:57 pm


The ?-defensin salt-bridge induces backbone stability to facilitate folding and confer proteolytic resistance

Abstract  
Salt-bridge interactions between acidic and basic amino acids contribute to the structural stability of proteins and to protein–protein interactions. A conserved salt-bridge is a canonical feature of the ?-defensin antimicrobial peptide family, but the role of this common structural element has not been fully elucidated. We have investigated mouse Paneth cell ?-defensin cryptdin-4 (Crp4) and peptide variants with mutations at Arg7 or Glu15 residue positions to disrupt the salt-bridge and assess the consequences on Crp4 structure, function, and stability. NMR analyses showed that both (R7G)-Crp4 and (E15G)-Crp4 adopt native-like structures, evidence of fold plasticity that allows peptides to reshuffle side chains and stabilize the structure in the absence of the salt-bridge. In contrast, introduction of a large hydrophobic side chain at position 15, as in (E15L)-Crp4 cannot be accommodated in the context of the Crp4 primary structure. Regardless of which side of the salt-bridge was mutated, salt-bridge variants retained bactericidal peptide activity with differential microbicidal effects against certain bacterial cell targets, confirming that the salt-bridge does not determine bactericidal activity per se. The increased structural flexibility induced by salt-bridge disruption enhanced peptide sensitivity to proteolysis. Although sensitivity to proteolysis by MMP7 was unaffected by most Arg7 and Glu15 substitutions, every salt-bridge variant was degraded extensively by trypsin. Moreover, the salt-bridge facilitates adoption of the characteristic ?-defensin fold as shown by the impaired in vitro refolding of (E15D)-proCrp4, the most conservative salt-bridge disrupting replacement. In Crp4, therefore, the canonical ?-defensin salt-bridge facilitates adoption of the characteristic ?-defensin fold, which decreases structural flexibility and confers resistance to degradation by proteinases.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-13
  • DOI 10.1007/s00726-012-1220-3
  • Authors
    • Håkan S. Andersson, School of Natural Sciences, Linnaeus University, 39182 Kalmar, Sweden
    • Sharel M. Figueredo, Department of Pathology and Laboratory Medicine, Keck School of Medicine of USC, USC/Norris Cancer Center, Los Angeles, CA 90089-9601, USA
    • Linda M. Haugaard-Kedström, School of Natural Sciences, Linnaeus University, 39182 Kalmar, Sweden
    • Elina Bengtsson, School of Natural Sciences, Linnaeus University, 39182 Kalmar, Sweden
    • Norelle L. Daly, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
    • Xiaoqing Qu, Department of Pathology and Laboratory Medicine, Keck School of Medicine of USC, USC/Norris Cancer Center, Los Angeles, CA 90089-9601, USA
    • David J. Craik, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
    • André J. Ouellette, Department of Pathology and Laboratory Medicine, Keck School of Medicine of USC, USC/Norris Cancer Center, Los Angeles, CA 90089-9601, USA
    • K. Johan Rosengren, School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 28 January 2012 | 5:51 pm


Decreased glutamate, glutamine and citrulline concentrations in plasma and muscle in endotoxemia cannot be reversed by glutamate or glutamine supplementation: a primary intestinal defect?

Abstract  
Endotoxemia affects intestinal physiology. A decrease of circulating citrulline concentration is considered as a reflection of the intestinal function. Citrulline can be produced in enterocytes notably from glutamate and glutamine. The aim of this work was to determine if glutamate, glutamine and citrulline concentrations in blood, intestine and muscle are decreased by endotoxemia, and if supplementation with glutamate or glutamine can restore normal concentrations. We induced endotoxemia in rats by an intraperitoneal injection of 0.3 mg kg?1 lipopolysaccharide (LPS). This led to a rapid anorexia, negative nitrogen balance and a transient increase of the circulating level of IL-6 and TNF-?. When compared with the values measured in pair fed (PF) animals, almost all circulating amino acids (AA) including citrulline decreased, suggesting a decrease of intestinal function. However, at D2 after LPS injection, most circulating AA concentrations were closed to the values recorded in the PF group. At that time, among AA, only glutamate, glutamine and citrulline were decreased in gastrocnemius muscle without change in intestinal mucosa. A supplementation with 4% monosodium glutamate (MSG) or an isomolar amount of glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscle. However, MSG supplementation led to an accumulation of glutamate in the intestinal mucosa. In conclusion, endotoxemia rapidly but transiently decreased the circulating concentrations of almost all AA and more durably of glutamate, glutamine and citrulline in muscle. Supplementation with glutamate or glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscles. The implication of a loss of the intestinal capacity for AA absorption and/or metabolism in endotoxemia (as judged from decreased citrulline plasma concentration) for explaining such results are discussed.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-14
  • DOI 10.1007/s00726-012-1221-2
  • Authors
    • Claire Boutry, INRA, CNRH-IdF, UMR914 Nutrition Physiology and Ingestive Behavior, 16 rue Claude Bernard, 75005 Paris, France
    • Hideki Matsumoto, Umami Wellness Research Group, Frontier Research Laboratory, Institute for Innovation, Ajinomoto Co. Inc, Kawasaki, 210-8681 Japan
    • Cécile Bos, INRA, CNRH-IdF, UMR914 Nutrition Physiology and Ingestive Behavior, 16 rue Claude Bernard, 75005 Paris, France
    • Christophe Moinard, Laboratory of Biological Nutrition, EA 2498, Faculté de Pharmacie-Université Paris Descartes, 75270 Paris Cedex 06, France
    • Luc Cynober, Laboratory of Biological Nutrition, EA 2498, Faculté de Pharmacie-Université Paris Descartes, 75270 Paris Cedex 06, France
    • Yulong Yin, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125 Hunan, China
    • Daniel Tomé, INRA, CNRH-IdF, UMR914 Nutrition Physiology and Ingestive Behavior, 16 rue Claude Bernard, 75005 Paris, France
    • François Blachier, INRA, CNRH-IdF, UMR914 Nutrition Physiology and Ingestive Behavior, 16 rue Claude Bernard, 75005 Paris, France
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 27 January 2012 | 6:55 pm


Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs

Abstract  
The ability of carnosine to prevent advanced glycoxidation end products (AGEs) and advanced lipoxidation end products (ALEs) formation, on the one hand, and the convincing evidence that these compounds act as pathogenetic factors, on the other hand, strongly support carnosine as a promising therapeutic agent for oxidative-based diseases. The mechanism/s by which carnosine inhibits AGEs and ALEs is still under investigation but an emerging hypothesis is that carnosine acts by deactivating the AGEs and ALEs precursors and in particular the reactive carbonyl species (RCS) generated by both lipid and sugar oxidation. The ability of carnosine to inhibit AGEs and ALEs formation and the corresponding biological effects has been demonstrated in several in vitro studies and in some animal models. However, such effects are in line of principle, limited in humans, due to the effect of serum carnosinase (absent in rodents), which catalyzes the carnosine hydrolysis to its constitutive amino acids. Such a limitation has prompted a great interest in the design of carnosine derivatives, which maintaining (or improving) the reactivity with RCS, are more resistant to carnosinase. The present paper intends to critically review the most recent studies oriented to obtaining carnosine derivatives, optimized in terms of reactivity with RCS, selectivity (no reaction with physiological aldehydes) and the pharmacokinetic profile (mainly through an enhanced resistance to carnosinase hydrolysis). The review also includes a brief description of AGEs and ALEs as drug targets and the evidence so far reported regarding the ability of carnosine as inhibitor of AGEs and ALEs formation and the proposed reaction mechanisms.

  • Content Type Journal Article
  • Category Review Article
  • Pages 1-16
  • DOI 10.1007/s00726-012-1224-z
  • Authors
    • Giulio Vistoli, Department of Pharmaceutical Sciences “Pietro Pratesi”, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy
    • Marina Carini, Department of Pharmaceutical Sciences “Pietro Pratesi”, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy
    • Giancarlo Aldini, Department of Pharmaceutical Sciences “Pietro Pratesi”, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 27 January 2012 | 6:55 pm


Insilico study of the A2AR–D2R kinetics and interfacial contact surface for heteromerization

Abstract  
G-protein-coupled receptors (GPCRs) are cell surface receptors. The dynamic property of receptor–receptor interactions in GPCRs modulates the kinetics of G-protein signaling and stability. In the present work, the structural and dynamic study of A2AR–D2R interactions was carried to acquire the understanding of the A2AR–D2R receptor activation and deactivation process, facilitating the design of novel drugs and therapeutic target for Parkinson’s disease. The structure-based features (Alpha, Beta, SurfAlpha, and SurfBeta; GapIndex, Leakiness and Gap Volume) and slow mode model (ENM) facilitated the prediction of kinetics (K off, K on, and K d) of A2AR–D2R interactions. The results demonstrated the correlation coefficient 0.294 for K d and K on and the correlation coefficient 0.635 for K d and K off, and indicated stable interfacial contacts in the formation of heterodimer. The coulombic interaction involving the C-terminal tails of the A2AR and intracellular loops (ICLs) of D2R led to the formation of interfacial contacts between A2AR–D2R. The properties of structural dynamics, ENM and KFC server-based hot-spot analysis illustrated the stoichiometry of A2AR–D2R contact interfaces as dimer. The propensity of amino acid residues involved in A2AR–D2R interaction revealed the presence of positively (R, H and K) and negatively (E and D) charged structural motif of TMs and ICL3 of A2AR and D2R at interface of dimer contact. Essentially, in silico structural and dynamic study of A2AR–D2R interactions will provide the basic understanding of the A2AR–D2R interfacial contact surface for activation and deactivation processes, and could be used as constructive model to recognize the protein–protein interactions in receptor assimilations.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-14
  • DOI 10.1007/s00726-012-1218-x
  • Authors
    • Amresh Prakash, Medicinal Chemistry Division, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi, 110007 India
    • Pratibha Mehta Luthra, Medicinal Chemistry Division, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi, 110007 India
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 25 January 2012 | 7:05 pm


Oxidative stress improvement is associated with increased levels of taurine in CKD patients undergoing lipid-lowering therapy

Abstract  
Lipid-lowering therapy has been reported to reduce several oxidative stress (OS) markers in hypercholesterolemia. Since OS is frequently associated with renal dysfunction, we aimed to investigate the effect of hypolipidemic drugs on oxidative stress and plasma taurine (Tau), a sulfur amino acid with a marked antioxidant effect, in chronic kidney disease (CKD). We enrolled 30 CKD randomized to receive three different hypolipidemic regimens for 12 months: simvastatin alone (40 mg/day) or ezetimibe/simvastatin combined therapy (10/20 or 10/40 mg/day). Low molecular weight (LMW) thiols including homocysteine, cysteine, cysteinylglycine, glutathione, and glutamylcysteine in their reduced and total form and oxidative stress indices as malondialdehyde (MDA) and allantoin/uric acid (All/UA) ratio were also evaluated. Tau concentration significantly increased throughout the therapy. The rise of taurine was more striking for the group with the concomitant administration of ezetimibe/simvastatin 10/40 mg/day (+31.6% after 1 year of therapy). A significant decrease of both MDA and All/UA ratio was observed during therapy for all patients (?19% for both MDA and All/UA ratio) with a more pronounced effect in patients treated with ezetimibe/simvastatin 10/40 mg/day (?26% for MDA and ?28% for All/UA ratio). Besides, an increase of thiols reduced forms was found (+20.7% of LMW thiols redox status) with a greater effect in subjects treated with ezetimibe/simvastatin 10/40 mg/day (+24.7%). Moreover, we demonstrated that oxidative stress improvement during therapy was correlated with increased taurine levels. We hypothesize that taurine may be responsible for the oxidative stress improvement observed during lipid-lowering treatment through the reduction of superoxide anion production at the respiratory chain activity level.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-9
  • DOI 10.1007/s00726-012-1223-0
  • Authors
    • Angelo Zinellu, Porto Conte Ricerche Srl, Tramariglio, Alghero, Sassari, Italy
    • Salvatore Sotgia, Department of Biomedical Sciences and Centre of Excellence for Biotechnology Development and Biodiversity Research, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
    • Giacomina Loriga, Department of Internal Medicine, Azienda Ospedaliera Universitaria, University of Sassari, Sassari, Italy
    • Luca Deiana, Department of Biomedical Sciences and Centre of Excellence for Biotechnology Development and Biodiversity Research, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
    • Andrea Ercole Satta, Department of Internal Medicine, Azienda Ospedaliera Universitaria, University of Sassari, Sassari, Italy
    • Ciriaco Carru, Department of Biomedical Sciences and Centre of Excellence for Biotechnology Development and Biodiversity Research, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 25 January 2012 | 7:05 pm


Activation of the transcription factor Nrf2 in macrophages, Caco-2 cells and intact human gut tissue by Maillard reaction products and coffee

Abstract  
In addition to direct antioxidative effects, Maillard reaction products (MRPs) could increase the antioxidative capacity of cells through the induction of cytoprotective enzymes. Since many of those enzymes are regulated by the transcription factor Nrf2, the effect of MRPs on nuclear translocation of Nrf2 in macrophages and Caco-2 cells was investigated. Stimulation of both cell types by MRPs showed a concentration-dependent significant increase in nuclear translocation of Nrf2 up to fivefold after short-term (2 h) and up to 50-fold after long-term treatment (24 h). In intact human gut tissue, nuclear translocation of Nrf2 was significantly twofold increased after short-term incubation. To study the activation mechanisms, macrophages and Caco-2 cells were stimulated with MRPs in the presence of catalase, which significantly suppressed Nrf2 activation. Thus, activation was related to extracellular H2O2 continuously formed from MRPs. Short-term incubation with coffee, a MRP-rich beverage, led to a trend towards Nrf2 activation in macrophages, but not in Caco-2 cells or intact human gut tissue. Long-term incubation with coffee (1–4 mg/mL) significantly increased nuclear Nrf2 up to 17-fold. Since raw coffee was inactive under the tested conditions, the effect was related to roasting products. Coffee-induced Nrf2 translocation was, however, only slightly reversed by catalase. Therefore, the Nrf2 activity of coffee can only partially be explained by MRP-induced, H2O2-dependent mechanisms. Thus, it can be concluded that MRPs may increase the antioxidative capacity inside the cell by inducing Nrf2-regulated signalling pathways not only in different cell types, but also in intact gut tissue.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-13
  • DOI 10.1007/s00726-012-1222-1
  • Authors
    • Tanja Sauer, Department of Chemistry and Pharmacy, Food Chemistry, Emil Fischer Center, Friedrich-Alexander University, Schuhstr. 19, 91052 Erlangen, Germany
    • Martin Raithel, Functional Tissue Diagnostics, Gastroenterology, Department of Medicine I, Friedrich-Alexander University, Ulmenweg 18, 91054 Erlangen, Germany
    • Jürgen Kressel, Functional Tissue Diagnostics, Gastroenterology, Department of Medicine I, Friedrich-Alexander University, Ulmenweg 18, 91054 Erlangen, Germany
    • Gerald Münch, Department of Pharmacology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW 2751, Australia
    • Monika Pischetsrieder, Department of Chemistry and Pharmacy, Food Chemistry, Emil Fischer Center, Friedrich-Alexander University, Schuhstr. 19, 91052 Erlangen, Germany
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 24 January 2012 | 7:15 pm


Effects of ?-alanine supplementation on exercise performance: a meta-analysis

Abstract  
Due to the well-defined role of ?-alanine as a substrate of carnosine (a major contributor to H+ buffering during high-intensity exercise), ?-alanine is fast becoming a popular ergogenic aid to sports performance. There have been several recent qualitative review articles published on the topic, and here we present a preliminary quantitative review of the literature through a meta-analysis. A comprehensive search of the literature was employed to identify all studies suitable for inclusion in the analysis; strict exclusion criteria were also applied. Fifteen published manuscripts were included in the analysis, which reported the results of 57 measures within 23 exercise tests, using 18 supplementation regimes and a total of 360 participants [174, ?-alanine supplementation group (BA) and 186, placebo supplementation group (Pla)]. BA improved (P = 0.002) the outcome of exercise measures to a greater extent than Pla [median effect size (IQR): BA 0.374 (0.140–0.747), Pla 0.108 (?0.019 to 0.487)]. Some of that effect might be explained by the improvement (P = 0.013) in exercise capacity with BA compared to Pla; no improvement was seen for exercise performance (P = 0.204). In line with the purported mechanisms for an ergogenic effect of ?-alanine supplementation, exercise lasting 60–240 s was improved (P = 0.001) in BA compared to Pla, as was exercise of >240 s (P = 0.046). In contrast, there was no benefit of ?-alanine on exercise lasting <60 s (P = 0.312). The median effect of ?-alanine supplementation is a 2.85% (?0.37 to 10.49%) improvement in the outcome of an exercise measure, when a median total of 179 g of ?-alanine is supplemented.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-13
  • DOI 10.1007/s00726-011-1200-z
  • Authors
    • R. M. Hobson, Biomedical, Life and Health Sciences Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS UK
    • B. Saunders, Biomedical, Life and Health Sciences Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS UK
    • G. Ball, Biomedical, Life and Health Sciences Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS UK
    • R. C. Harris, Junipa Ltd, Newmarket, Suffolk, UK
    • C. Sale, Biomedical, Life and Health Sciences Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS UK
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 24 January 2012 | 8:28 am


Synthesis and aggregation properties of a novel enzymatically resistant nucleoamino acid

Abstract  
In this work, we describe the synthesis, evaluation of some biological properties, such as DNA- and RNA-binding ability and in sero stability, as well as the supramolecular assembly of a novel nucleoamino acid based on l-spinacine. More particularly, a thymine-containing l-spinacine derivative was synthesized in liquid phase by a simple peptide-coupling procedure. Subsequently, nucleic acid and Cu2+-binding ability, as well as self-assembly properties of the novel nucleoamino acid, were investigated by spectroscopy (CD and UV) and laser light scattering which furnished interesting information on the assembly of supramolecular networks based on the peptidyl nucleoside analog. Finally, nucleoamino acid enzymatic stability was studied and a half life of about 7 days was found in the presence of fresh human serum.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-6
  • DOI 10.1007/s00726-012-1219-9
  • Authors
    • Giovanni N. Roviello, Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Naples, Italy
    • Anna Mottola, Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Naples, Italy
    • Domenica Musumeci, Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Naples, Italy
    • Enrico M. Bucci, Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Naples, Italy
    • Carlo Pedone, Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Naples, Italy
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 18 January 2012 | 7:59 am


Cytotoxic activity of new racemic and optically active N-phosphonoalkyl bicyclic ?-amino acids against human malignant cell lines

Abstract  
The cytotoxic effects of novel racemic and optically active constrained N-phosphonoalkyl bicyclic ?-amino acids were tested against a panel of human tumor cell lines. All of the compounds investigated exhibited different concentration-dependent antiproliferative effects against the HT-29, MDA-MB-231, HepG2 and HeLa cell lines after 24 h treatment. The most sensitive cells were the HeLa cells at various concentrations of the four compounds tested. The aminophosphonate 3 exerted the most pronounced antiproliferative effect against the HeLa cells (inhibition of the cell vitality up to 70% at 0.5 mg/ml) and was not toxic to the normal Lep3 cells at lower concentration. Furthermore, the N-phosphonophenyl derivatives 1 and 2 displayed antiproliferative effect against mainly the MDA-MB-231 tumour cells at higher concentration.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-6
  • DOI 10.1007/s00726-012-1217-y
  • Authors
    • Petar T. Todorov, Department of Organic Chemistry, University of Chemical Technology and Metallurgy, 1756 Sofia, Bulgaria
    • Diana W. Wesselinova, Institute of Experimental Morphology, Pathology and Anthropology with Muzeum, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Bl. 25, 1113 Sofia, Bulgaria
    • Nikola D. Pavlov, Department of Organic Chemistry, University of Chemical Technology and Metallurgy, 1756 Sofia, Bulgaria
    • Jean Martinez, Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS-Université Montpellier 1 et 2, Université Montpellier 2, place E. Bataillon, 34095 Montpellier Cedex 5, France
    • Monique Calmes, Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS-Université Montpellier 1 et 2, Université Montpellier 2, place E. Bataillon, 34095 Montpellier Cedex 5, France
    • Emilia D. Naydenova, Department of Organic Chemistry, University of Chemical Technology and Metallurgy, 1756 Sofia, Bulgaria
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 11 January 2012 | 6:57 pm


The role of TG2 in ECV304-related vasculogenic mimicry

Abstract  
Tumour vasculogenesis can occur by a process referred to as vasculogenic mimicry, whereby the vascular structures are derived from the tumour itself. These tumours are highly aggressive and do not respond well to anti-angiogenic therapy. Here, we use the well characterised ECV304 cell line, now known as the bladder cancer epithelial cell line T24/83 which shows both epithelial and endothelial characteristics, as a model of in vitro vasculogenic mimicry. Using optimised ratios of co-cultures of ECV304 and C378 human fibroblasts, tubular structures were identifiable after 8 days. The tubular structures showed high levels of TG2 antigen and TG in situ activity. Tubular structures and in situ activity could be blocked either by site-directed irreversible inhibitors of TG2 or by silencing the ECV304 TG2 by antisense transfection. In situ activity for TG2 showed co-localisation with both fibronectin and collagen IV. Deposition of these proteins into the extracellular matrix could be reduced by inclusion of non-cell penetrating TG inhibitors when analysed by Western blotting suggesting that the contribution of TG2 to tube formation is extracellular. Incubation of ECV304 cells with these same irreversible inhibitors reduced cell migration which paralleled a loss in focal adhesion assembly, actin cytoskeleton formation and fibronectin deposition. TG2 appears essential for ECV304 tube formation, thus representing a potential novel therapeutic target in the inhibition of vasculogenic mimicry.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-13
  • DOI 10.1007/s00726-011-1214-6
  • Authors
    • Richard A. Jones, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK
    • Zhuo Wang, School of Life and Health Sciences, Aston University, Birmingham, B4 7ET UK
    • Shakthi Dookie, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK
    • Martin Griffin, School of Life and Health Sciences, Aston University, Birmingham, B4 7ET UK
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 9 January 2012 | 8:38 pm


Cis–trans peptide variations in structurally similar proteins

Abstract  
The presence of energetically less favourable cis peptides in protein structures has been observed to be strongly associated with its structural integrity and function. Inter-conversion between the cis and trans conformations also has an important role in the folding process. In this study, we analyse the extent of conservation of cis peptides among similar folds. We look at both the amino acid preferences and local structural changes associated with such variations. Nearly 34% of the Xaa-Proline cis bonds are not conserved in structural relatives; Proline also has a high tendency to get replaced by another amino acid in the trans conformer. At both positions bounding the peptide bond, Glycine has a higher tendency to lose the cis conformation. The cis conformation of more than 30% of ? turns of type VIb and IV are not found to be conserved in similar structures. A different view using Protein Block-based description of backbone conformation, suggests that many of the local conformational changes are highly different from the general local structural variations observed among structurally similar proteins. Changes between cis and trans conformations are found to be associated with the evolution of new functions facilitated by local structural changes. This is most frequent in enzymes where new catalytic activity emerges with local changes in the active site. Cistrans changes are also seen to facilitate inter-domain and inter-protein interactions. As in the case of folding, cistrans conversions have been used as an important driving factor in evolution.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-13
  • DOI 10.1007/s00726-011-1211-9
  • Authors
    • Agnel Praveen Joseph, INSERM UMR-S 665, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Université Denis Diderot-Paris 7, INTS, 6, rue Alexandre Cabanel, 75739 Paris Cedex 15, France
    • Narayanaswamy Srinivasan, Molecular Biophysics Unit, Indian Institute of Science, 560012 Bangalore, India
    • Alexandre G. de Brevern, INSERM UMR-S 665, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Université Denis Diderot-Paris 7, INTS, 6, rue Alexandre Cabanel, 75739 Paris Cedex 15, France
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 7 January 2012 | 5:55 pm


Metabolism and neurotoxicity of homocysteine thiolactone in mice: protective role of bleomycin hydrolase

Abstract  
Genetic or nutritional disorders in homocysteine (Hcy) metabolism elevate Hcy-thiolactone and cause heart and brain diseases. Hcy-thiolactone has been implicated in these diseases because it has the ability to modify protein lysine residues and generate toxic N-Hcy-proteins with auto-immunogenic, pro-thrombotic, and amyloidogenic properties. Bleomycin hydrolase (Blmh) has the ability to hydrolyze l-Hcy-thiolactone (but not d-Hcy-thiolactone) to Hcy in vitro, but whether this reflects a physiological function has been unknown. Here, we show that Blmh ?/? mice excreted in urine 1.8-fold more Hcy-thiolactone than wild-type Blmh +/+ animals (P = 0.02). Hcy-thiolactone was elevated 2.3-fold in brains (P = 0.004) and 2.0-fold in kidneys (P = 0.047) of Blmh ?/? mice relative to Blmh +/+ animals. Plasma N-Hcy-protein was elevated in Blmh ?/? mice fed a normal (2.3-fold, P < 0.001) or hyperhomocysteinemic diet (1.5-fold, P < 0.001), compared with Blmh +/+ animals. More intraperitoneally injected l-Hcy-thiolactone was recovered in plasma in Blmh ?/? mice than in wild-type Blmh +/+ animals (83.1 vs. 39.3 ?M, P < 0.0001). In Blmh +/+ mice injected intraperitoneally with d-Hcy-thiolactone, d,l-Hcy-thiolactone, or l-Hcy-thiolactone, 88, 47, or 6.3%, respectively, of the injected dose was recovered in plasma. The incidence of seizures induced by l-Hcy-thiolactone injections (3,700 nmol/g body weight) was higher in Blmh ?/? than in Blmh +/+ mice (93.8 vs. 29.5%, P < 0.001). Using the Blmh null mice, we provide the first direct evidence that a specific Hcy metabolite, Hcy-thiolactone, rather than Hcy itself, is neurotoxic in vivo. Taken together, our findings indicate that Blmh protects mice against l-Hcy-thiolactone toxicity by metabolizing it to Hcy and suggest a mechanism by which Blmh might protect against neurodegeneration associated with hyperhomocysteinemia and Alzheimer’s disease.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-10
  • DOI 10.1007/s00726-011-1207-5
  • Authors
    • Kamila Borowczyk, Department of Microbiology and Molecular Genetics, International Center for Public Health, UMDNJ-New Jersey Medical School, 225 Warren Street, Newark, NJ 07101, USA
    • Joanna Tiso?czyk, Department of Microbiology and Molecular Genetics, International Center for Public Health, UMDNJ-New Jersey Medical School, 225 Warren Street, Newark, NJ 07101, USA
    • Hieronim Jakubowski, Department of Microbiology and Molecular Genetics, International Center for Public Health, UMDNJ-New Jersey Medical School, 225 Warren Street, Newark, NJ 07101, USA
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 7 January 2012 | 5:55 pm


Monosodium glutamate intake increases hemoglobin level over 5 years among Chinese adults

Abstract  
The aim of this analysis was to determine the relationship between monosodium glutamate (MSG) intake and change in hemoglobin (Hb) levels and the risk of anemia over 5 years in 1197 Chinese men and women who participated in the Jiangsu Nutrition Study (JIN). MSG intake and Hb were quantitatively assessed in 2002 and followed up in 2007. Diet and lifestyle factors were assessed at both time points. There was a positive association between MSG intake and increase in Hb among men but not women. In the multivariate model adjusting for demographic and lifestyle factors as well as baseline dietary pattern, the beta values and 95% confidence interval for Hb changes across quartiles of MSG intake were 0, 0.67(0.04–1.29), 0.99(0.38–1.60), 0.73(0.13–1.34) among men (p for trend 0.091); 0, ?0.01(?0.45–0.43), 0.23(?0.25–0.71), and ?0.45(?0.96–0.05) among women (p for trend 0.087). Among anemic participants at baseline, there was a significant inverse association between MSG intake and the risk of anemia at follow-up. Comparing extreme quartiles of MSG intake among those anemic at baseline, the relative risk for persistent anemia at follow-up was 0.49 (95% CI: 0.28–0.86, p < 0.01). The association was independent of dietary patterns and lifestyle factors. A dose–response relationship between MSG intake and increase in Hb levels among anemic participants was seen. MSG intake may have independent Hb-increasing effects, especially among men and those anemic at baseline.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-9
  • DOI 10.1007/s00726-011-1213-7
  • Authors
    • Zumin Shi, Department of Nutrition and Foodborne Disease Prevention, Jiangsu Provincial Centre for Disease Control and Prevention, 172 Jiangsu Road, Nanjing, 210009 China
    • Baojun Yuan, Department of Nutrition and Foodborne Disease Prevention, Jiangsu Provincial Centre for Disease Control and Prevention, 172 Jiangsu Road, Nanjing, 210009 China
    • Anne W. Taylor, Discipline of Medicine, University of Adelaide, Adelaide, SA 5000, South Australia
    • Eleonora Dal Grande, Discipline of Medicine, University of Adelaide, Adelaide, SA 5000, South Australia
    • Gary A. Wittert, Discipline of Medicine, University of Adelaide, Adelaide, SA 5000, South Australia
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 5 January 2012 | 6:03 pm


Diffuse reflectance spectroscopy of fibrous proteins

Abstract  
UV–visible diffuse reflectance (DR) spectra of the fibrous proteins wool and feather keratin, silk fibroin and bovine skin collagen are presented. Natural wool contains much higher levels of visible chromophores across the whole visible range (700–400 nm) than the other proteins and only those above 450 nm are effectively removed by bleaching. Both oxidative and reductive bleaching are inefficient for removing yellow chromophores (450–400 nm absorbers) from wool. The DR spectra of the four UV-absorbing amino acids tryptophan, tyrosine, cystine and phenylalanine were recorded as finely ground powders. In contrast to their UV–visible spectra in aqueous solution where tryptophan and tyrosine are the major UV absorbing species, surprisingly the disulphide chromophore of solid cystine has the strongest UV absorbance measured using the DR remission function F(R)?. The DR spectra of unpigmented feather and wool keratin appear to be dominated by cystine absorption near 290 nm, whereas silk fibroin appears similar to tyrosine. Because cystine has a flat reflectance spectrum in the visible region from 700 to 400 nm and the powder therefore appears white, cystine absorption does not contribute to the cream colour of wool despite the high concentration of cystine residues near the cuticle surface. The disulphide absorption of solid l-cystine in the DR spectrum at 290 nm is significantly red shifted by ~40 nm relative to its wavelength in solution, whereas homocystine and lipoic acid showed smaller red shifts of 20 nm. The large red shift observed for cystine and the large difference in intensity of absorption in its UV–visible and DR spectra may be due to differences in the dihedral angle between the crystalline solid and the solvated molecules in solution.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-9
  • DOI 10.1007/s00726-011-1201-y
  • Authors
    • Keith R. Millington, CSIRO Materials Science and Engineering, Belmont, VIC 3216, Australia
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 4 January 2012 | 6:01 pm


Molecular mechanism underlying the cerebral effect of Gly-Pro-Glu tripeptide bound to l-dopa in a Parkinson’s animal model

Abstract  
Oxidative stress is a critical contributing factor to neurodegenerative disorders. Therefore, the inhibition of ROS formation, responsible for chronic detrimental neuroinflammation, is an important strategy for preventing the neurodegenerative disease and for neuroprotective therapy. Gly-Pro-Glu (GPE) is the N-terminal tripeptide of insulin-like growth factor-I, which is naturally cleaved in the plasma and brain tissues. GPE has neuroprotective effects since it crosses the blood–CSF and the functional CSF–brain barriers and binds to glial cells. It has been shown that GPE improves motor behaviour in rats after 6-OHDA lesion, although it does not rescue dopaminergic neurons. Thus, we hypothesized that the GPE therapeutic efficacy in a Parkinson model might be improved by combining GPE to l-dopa. Here, we used an animal model that represents a progressive chronic Parkinson’s disease (PD) model, characterized by high levels of oxidative stress and inflammation. We showed that the co-drug, in which l-dopa is covalently linked to the GPE tripeptide, by down-regulating the expression of inflammatory genes, decreases the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced inflammatory response and, by up-regulating tyrosine hydroxylase, reduces MPTP-induced neurotoxicity. Furthermore, by determining the nuclear translocation/activation of Nrf2 and NF-?B, we showed that systemic administration of the co-drug activates Nrf2-induced antioxidant response while suppressing NF-?B inflammatory pathway. Data suggest that the binding of l-dopa to GPE tripeptide might represent a promising strategy to supply l-dopa to parkinsonian patients.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-9
  • DOI 10.1007/s00726-011-1210-x
  • Authors
    • Alba Minelli, Dipartimento Medicina Sperimentale Scienze Biochimiche, Sezione Biochimica Cellulare, Università di Perugia, Via del Giochetto, 06124 Perugia, Italy
    • C. Conte, Dipartimento Medicina Sperimentale Scienze Biochimiche, Sezione Biochimica Cellulare, Università di Perugia, Via del Giochetto, 06124 Perugia, Italy
    • I. Cacciatore, Dipartimento di Scienze del Farmaco, Università “G. D’Annunzio”, Via dei Vestini 31, 66100 Chieti, Italy
    • C. Cornacchia, Dipartimento di Scienze del Farmaco, Università “G. D’Annunzio”, Via dei Vestini 31, 66100 Chieti, Italy
    • F. Pinnen, Dipartimento di Scienze del Farmaco, Università “G. D’Annunzio”, Via dei Vestini 31, 66100 Chieti, Italy
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 4 January 2012 | 6:01 pm


Lyophilization is suitable for storage and shipment of fresh tissue samples without altering RNA and protein levels stored at room temperature

Abstract  
Lyophilization has been widely used for preservation, such as in food industry, pharmacy, biotechnology and tissues engineering, etc. However, there is no report on whether it could affect stability of RNA and protein levels in biological tissue samples. Herein we show that lyophilization can be used for storage of biological tissue samples without loss of bioactivities even stored at room temperature for 7–14 days. To address this issue, C57BL mouse tissues were prepared and dried by lyophilization and a baking method, respectively, followed by examination of morphological structure and total proteins by SDS-PAGE as well as gelatin zymography. Subsequently, the stability of RNAs and proteins, which were lyophilized and stored at room temperature (23°C) for 14 days was further examined by RT-PCR, SDS-PAGE and western blot. Results demonstrated that lyophilization did not alter total protein activities of various tissues, including enzyme activities, immunoreactivities and phosphorylation, and did not affect several RNAs in lyophilized tissues. Taken together, lyophilization may represent a valuable approach for preservation and long-distance shipment of biological samples, particularly for the international exchange of biological samples without altering their bioactivities.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-6
  • DOI 10.1007/s00726-011-1212-8
  • Authors
    • Yonghong Wu, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing Institute of Radiation Medicine, Beijing, 100850 China
    • Min Wu, Department of Genetics, Graduate School of Peking Union Medical College, Beijing, 100081 China
    • Yanchun Zhang, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing Institute of Radiation Medicine, Beijing, 100850 China
    • Weiguang Li, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing Institute of Radiation Medicine, Beijing, 100850 China
    • Yan Gao, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing Institute of Radiation Medicine, Beijing, 100850 China
    • Zhihui Li, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing Institute of Radiation Medicine, Beijing, 100850 China
    • Zhaoyan Wang, Department of Ophthalmology, General Hospital of Chinese PLA, Beijing, 100853 China
    • Gert Lubec, Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18, 1090 Vienna, Austria
    • Chenggang Zhang, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing Institute of Radiation Medicine, Beijing, 100850 China
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 4 January 2012 | 8:00 am


Comparative syntheses of peptides and peptide thioesters derived from mouse and human prion proteins

Abstract  
Prions are suspected as causative agents of several neuropathogenic diseases, even though the mode of their action is still not clear. A combination of chemical and recombinant syntheses can provide suitable probes for explanation of prions role in pathogenesis of neurodegenerative diseases. However, the prions contain several difficult sequences for synthesis by Fmoc/tBu approach. For that reason, the peptide thioesters as the key building blocks for chemical syntheses of proteins by native chemical ligation were employed. A scan of the mouse prion domain 93–231 was carried out in order to discover availability of derived thioesters as the suitable building blocks for a total chemical synthesis of the prion protein based probes. The synthesis on 2-chlorotritylchloride resin was utilized and after a deprotection of the samples for analysis, the peptide segments were purified and characterized. If the problems were detected during the synthesis, the segment was re-synthesized either using the special pseudoproline dipeptides or by splitting its molecule to two or three smaller segments, which were prepared easier. The protected segments, prepared correctly without any deletion and in sufficient amounts, were coupled either with EtSH after DIC/DMAP activation or with p-Ac-NH-Ph-SH using PyBOP activation to yield corresponding thioesters. In some special cases, the other techniques of thioester formation, like sulfonamide-safety catch and/or trimethylaluminium approach were utilized.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-13
  • DOI 10.1007/s00726-011-1203-9
  • Authors
    • Jaroslav Šebestík, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
    • Zbigniew Zawada, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
    • Martin Šafa?ík, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
    • Jan Hlavá?ek, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 2 January 2012 | 5:46 pm


N-Succinimidyl 4-[18F]-fluoromethylbenzoate-labeled dimeric RGD peptide for imaging tumor integrin expression

Abstract  
RGD peptides, radiolabeled with 18F, have been used in the clinic for PET imaging of tumor angiogenesis in cancer patients. RGD peptides are typically labeled using a prosthetic group such as N-succinimidyl 4-[18F]-fluorobenzoate ([18F]SFB) or 4-nitrophenyl 2-[18F]-fluoropropionate ([18F]NPFP). However, the complex radiosynthetic procedures have impeded their broad application in clinical studies. We previously radiolabeled proteins and peptides with the prosthetic group, N-succinimidyl 4-[18F]-fluoromethylbenzoate ([18F]SFMB), which was prepared in a simple one-step procedure. In this study, we labeled a PEGylated cyclic RGD peptide dimer, PEG3-E[c(RGDyK)]2 (PRGD2), using [18F]SFMB and evaluated for imaging tumor ?v?3 integrin expression with positron emission tomography (PET). [18F]SFMB was prepared in one step using [18F]fluoride displacement of a nitrobenzenesulfonate leaving group under mild reaction conditions followed by HPLC purification. The 18F-labeled peptide, [18F]FMBPRGD2 was prepared by coupling PRGD2 with [18F]SFMB in pH 8.6 borate buffer and purified with HPLC. The direct labeling on BMBPRGD2 was also attempted. A Siemens Inveon PET was used to image the uptake of the [18F]FMBPRGD2 into a U87MG xenograft mouse model. [18F]FMBPRGD2, was prepared with a 15% overall radiochemical yield (uncorrected) in a total synthesis time of 90 min, which was considerably shorter than the preparation of [18F]SFB- and [18F]NPFP-labeled RGD peptides. The direct labeling, however, was not successful. High quality microPET images using [18F]FMBPRGD2 clearly visualized tumors by 15 min with good target to background ratio. Early tracer accumulation in the bladder suggests fast renal clearance. No obvious bone uptake can be detected even at 4-h time point indicating that fluorine attachment is stable in mice. In conclusion, N-succinimidyl 4-[18F]-fluoromethylbenzoate ([18F]SFMB) prosthetic group can be a good alternative for labeling RGD peptides to image ?v?3 integrin expression and for labeling other peptides.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-9
  • DOI 10.1007/s00726-011-1208-4
  • Authors
    • Weihua Li, Department of Medical Imaging and Nuclear Medicine, Fourth Affiliated Hospital, Harbin Medical University, Harbin, 150001 China
    • Lixin Lang, Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 31 Center Drive, Suite 1C14, Bethesda, MD 20892-2281, USA
    • Gang Niu, Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 31 Center Drive, Suite 1C14, Bethesda, MD 20892-2281, USA
    • Ning Guo, Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 31 Center Drive, Suite 1C14, Bethesda, MD 20892-2281, USA
    • Ying Ma, Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 31 Center Drive, Suite 1C14, Bethesda, MD 20892-2281, USA
    • Dale O. Kiesewetter, Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 31 Center Drive, Suite 1C14, Bethesda, MD 20892-2281, USA
    • Baozhong Shen, Department of Medical Imaging and Nuclear Medicine, Fourth Affiliated Hospital, Harbin Medical University, Harbin, 150001 China
    • Xiaoyuan Chen, Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 31 Center Drive, Suite 1C14, Bethesda, MD 20892-2281, USA
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 30 December 2011 | 5:42 pm


Synthesis of biologically stable gold nanoparticles using imidazolium-based amino acid ionic liquids

Abstract  
A novel double-step reduction procedure for the synthesis of gold nanoparticles (AuNPs) using amino acid ionic liquids has been employed. 1-Dodecyl-3-methyl imidazolium tryptophan ([C12mim]Trp) and 1-ethyl-3-methyl imidazolium tryptophan ([C2mim]Trp) were used for this synthesis. The synthesized AuNPs were characterized by UV–vis spectroscopy, transmission electron microscopy and dynamic light scattering. The behavior of these AuNPs were also probed in a biological media. It was proven that AuNPs synthesized at [C12mim]Trp have more stability than AuNPs synthesized at [C2mim]Trp due to the longer alkyl chain of the imidazolium moiety. The solubility test shows that the resultant AuNPs have a hydrophilic nature. Finally, it was seen that due to the presence of a biomolecule, namely Trp, in the structure of AuNPs protecting shell, higher stability and biocompatibility was achieved in the biological media.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-8
  • DOI 10.1007/s00726-011-1205-7
  • Authors
    • Afsaneh Safavi, Department of Chemistry, College of Science, Shiraz University, Shiraz, 71454 Fars, Iran
    • Sedigheh Zeinali, Nanotechnology Research Institute, Shiraz University, Shiraz, Iran
    • Mahdieh Yazdani, Department of Chemistry, College of Science, Shiraz University, Shiraz, 71454 Fars, Iran
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 30 December 2011 | 5:42 pm


Oral intake of ?-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks

Abstract  
?-Aminobutyric acid (GABA) is a kind of amino acid contained in green tea leaves and other foods. Several reports have shown that GABA might affect brain protein synthesis, improve many brain functions such as memory and study capability, lower the blood pressure of spontaneously hypertensive rats, and may also have a relaxation effect in humans. However, the evidence for its mood-improving function is still not sufficient. In this study, we investigated how the oral intake of GABA influences human adults psychologically and physiologically under a condition of mental stress. Sixty-three adults (28 males, 35 females) participated in a randomized, single blind, placebo-controlled, crossover-designed study over two experiment days. Capsules containing 100 mg of GABA or dextrin as a placebo were used as test samples. The results showed that EEG activities including alpha band and beta band brain waves decreased depending on the mental stress task loads, and the condition of 30 min after GABA intake diminished this decrease compared with the placebo condition. That is to say, GABA might have alleviated the stress induced by the mental tasks. This effect also corresponded with the results of the POMS scores.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-7
  • DOI 10.1007/s00726-011-1206-6
  • Authors
    • A. Yoto, Laboratory of Nutritional Biochemistry and Global COE Program, University of Shizuoka, School of Food and Nutritional Sciences, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526 Japan
    • S. Murao, Laboratory of Nutritional Biochemistry and Global COE Program, University of Shizuoka, School of Food and Nutritional Sciences, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526 Japan
    • M. Motoki, Laboratory of Nutritional Biochemistry and Global COE Program, University of Shizuoka, School of Food and Nutritional Sciences, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526 Japan
    • Y. Yokoyama, Mitsubishi Corporation, Marunouchi Park BLDG, 6-1,Marunouchi 2-Chome, Chiyoda-Ku, Tokyo, 100-8086 Japan
    • N. Horie, Pharma Foods International Co. Ltd, 1-49 Goryo-Ohara, Nishikyo-ku, Kyoto, 615-8245 Japan
    • K. Takeshima, Pharma Foods International Co. Ltd, 1-49 Goryo-Ohara, Nishikyo-ku, Kyoto, 615-8245 Japan
    • K. Masuda, Pharma Foods International Co. Ltd, 1-49 Goryo-Ohara, Nishikyo-ku, Kyoto, 615-8245 Japan
    • M. Kim, Pharma Foods International Co. Ltd, 1-49 Goryo-Ohara, Nishikyo-ku, Kyoto, 615-8245 Japan
    • H. Yokogoshi, Laboratory of Nutritional Biochemistry and Global COE Program, University of Shizuoka, School of Food and Nutritional Sciences, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526 Japan
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 27 December 2011 | 5:50 pm


l-Arginine improves multiple physiological parameters in mice exposed to diet-induced metabolic disturbances

Abstract  
l-Arginine (l-Arg) is a conditionally essential amino acid and a natural constituent of dietary proteins. Studies in obese rats and type 2 diabetic humans have indicated that dietary supplementation with l-Arg can diminish gain in white adipose tissue (WAT) and improve insulin sensitivity. However, the effects of l-Arg on glucose homeostasis, body composition and energy metabolism remain unclear. In addition, no studies have, to our knowledge, examined whether l-Arg has beneficial effects as a dietary supplement in the mouse model. In the present study, we investigated the effects of l-Arg supplementation to male C57BL/6 mice on an array of physiological parameters. l-Arg supplemented mice were maintained on a low-protein diet and body composition, appetite regulation, glucose tolerance, insulin sensitivity and energy expenditure were evaluated. A significant reduction in epididymal WAT was observed in l-Arg supplemented mice compared with mice fed an isocaloric control diet. Surprisingly, the l-Arg supplemented animals were hyperphagic corresponding to a highly significant decrease in feed efficiency, as body weight developed in a similar pattern in both experimental groups. Glucose homeostasis experiments revealed a major effect of l-Arg supplementation on glucose tolerance and insulin sensitivity, interestingly, independent of a parallel regulation in whole-body adiposity. Increased l-Arg ingestion also raised energy expenditure; however, no concurrent effect on locomotor activity, substrate metabolism or expression of uncoupling proteins (UCP1 and UCP2) in adipose tissues was displayed. In conclusion, dietary l-Arg supplementation substantially affects an array of metabolic-associated parameters including a reduction in WAT, hyperphagia, improved insulin sensitivity and increased energy expenditure in mice fed a low-protein diet.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-11
  • DOI 10.1007/s00726-011-1199-1
  • Authors
    • Christoffer Clemmensen, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
    • Andreas N. Madsen, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2100 Copenhagen, Denmark
    • Sanela Smajilovic, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
    • Birgitte Holst, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2100 Copenhagen, Denmark
    • Hans Bräuner-Osborne, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 26 December 2011 | 5:46 pm


Glycation promotes the formation of genotoxic aggregates in glucose oxidase

Abstract  
This study investigates the effect of pentose sugars (ribose and arabinose) on the structural and chemical modifications in glucose oxidase (GOD) as well as genotoxic potential of this modified form. An intermediate state of GOD was observed on day 12 of incubation having CD minima peaks at 222 and 208 nm, characteristic of ?-helix and a few tertiary contacts with altered tryptophan environment and high ANS binding. All these features indicate the existence of molten globule state of the GOD with ribose and arabinose on day 12. GOD on day 15 of incubation forms ? structures as revealed by CD and FTIR which may be due to its aggregation. Furthermore, GOD on day 15 showed a remarkable increase in Thioflavin T fluorescence at 485 nm. Comet assay of lymphocytes and plasmid nicking assay in presence of glycated GOD show DNA damage which confirmed the genotoxicity of advance glycated end products. Hence, our study suggests that glycated GOD results in the formation of aggregates and the advanced glycated end products, which are genotoxic in nature.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-12
  • DOI 10.1007/s00726-011-1204-8
  • Authors
    • Taqi Ahmed Khan, Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202 002 India
    • Samreen Amani, Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202 002 India
    • Aabgeena Naeem, Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202 002 India
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 23 December 2011 | 5:54 pm


Tissue-specific responses to loss of transglutaminase 2

Abstract  
Of the eight catalytic transglutaminases (TGs), transglutaminase 2 (TG2) has been the most comprehensively studied due to its ubiquitous expression in multiple cell types. Despite the observed critical role for this enzyme in multiple biological processes in vitro, TG2 knockout mouse models have shown no severe developmental phenotypes, suggesting compensation by other TGs. To begin characterization of the compensating mechanisms, we analyzed total transamidating activity and expression patterns of all catalytically active TGs in seven different tissues/organs from wild-type and TG2 knockout mice. Inhibitory analysis with TG2-specific inhibitor KCC-009 suggests that relative contribution of TG2 in total transamidating activity differs in various tissues. Accordingly, our data indicate tissue-specific mechanisms of compensation for the loss of TG2, including transcriptional compensation in heart and liver versus functional compensation in aorta, kidney and skeletal/cartiagenous tissues. On the contrary, no compensation has been detected in skeletal muscle, suggesting a limited role for the TG2-mediated transamidation in normal development of this tissue.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-9
  • DOI 10.1007/s00726-011-1183-9
  • Authors
    • Stephanie Deasey, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    • Shobana Shanmugasundaram, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    • Maria Nurminskaya, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 22 December 2011 | 1:51 pm


Modulation of inflammatory pathways by the immune cholinergic system

Abstract  
Research done in the past years pointed to a novel function of cholinergic transmission. It has been shown that cholinergic transmission can modulate various aspects of the immune function, whether innate or adaptive. Cholinergic transmission affects immune cell proliferation, cytokine production, T helper differentiation and antigen presentation. Theses effects are mediated by cholinergic muscarinic and nicotinic receptors and other cholinergic components present in immune cells, such as acetylcholinesterase (AChE) and cholineacetyltransferase. The ?7 nicotinic acetylcholine receptor was designated anti-inflammatory activity and has shown promise in pre-clinical models of inflammatory disorders. We herein describe the various components of the immune cholinergic system, and specifically the immune suppressive effects of ?7 activation. This activation can be accomplished either by direct stimulation or indirectly, by inhibition of AChE. Thus, the presence of the immune cholinergic system can pave the way for novel immunomodulatory agents, or to the broadening of use of known cholinergic agents.

  • Content Type Journal Article
  • Category Invited Review
  • Pages 1-13
  • DOI 10.1007/s00726-011-1192-8
  • Authors
    • Eran Nizri, Department of General Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
    • Talma Brenner, Department of Neurology, Hadassah University Hospital and Hebrew University Medical School, P.O. Box 12000, 91120 Jerusalem, Israel
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 22 December 2011 | 1:51 pm


Changes in plasma phenylalanine, isoleucine, leucine, and valine are associated with significant changes in intracranial pressure and jugular venous oxygen saturation in patients with severe traumatic brain injury

Abstract  
Changes in plasma aromatic amino acids (AAA = phenylalanine, tryptophan, tyrosine) and branched chain amino acids (BCAA = isoleucine, leucine, valine) levels possibly influencing intracranial pressure (ICP) and cerebral oxygen consumption (SjvO2) were investigated in 19 sedated patients up to 14 days following severe traumatic brain injury (TBI). Compared to 44 healthy volunteers, jugular venous plasma BCAA were significantly decreased by 35% (p < 0.001) while AAA were markedly increased in TBI patients by 19% (p < 0.001). The BCAA to AAA ratio was significantly decreased by 55% (p < 0.001) which persisted during the entire study period. Elevated plasma phenylalanine was associated with decreased ICP and increased SjvO2, while higher plasma isoleucine and leucine levels were associated with increased ICP and higher plasma leucine and valine were linked to decreased SjvO2. The amount of enterally administered amino acids was associated with significantly increased plasma levels with the exception of phenylalanine. Contrary to the initial assumption that elevated AAA and decreased BCAA levels are detrimental, increased plasma phenylalanine levels were associated with beneficial signs in terms of decreased ICP and reduced cerebral oxygen consumption reflected by increased SjvO2; concomitantly, elevated plasma isoleucine and leucine levels were associated with increased ICP while leucine and valine were associated with decreased SjvO2 following severe TBI, respectively. The impact of enteral nutrition on this observed pattern must be examined prospectively to determine if higher amounts of phenylalanine should be administered to promote beneficial effects on brain metabolism and if normalization of plasma BCAA levels is without cerebral side effects.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-10
  • DOI 10.1007/s00726-011-1202-x
  • Authors
    • Raphael N. Vuille-Dit-Bille, Surgical Intensive Care Medicine, UniversitätsSpital Zürich, 8091 Zurich, Switzerland
    • Riem Ha-Huy, Surgical Intensive Care Medicine, UniversitätsSpital Zürich, 8091 Zurich, Switzerland
    • John F. Stover, Surgical Intensive Care Medicine, UniversitätsSpital Zürich, 8091 Zurich, Switzerland
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 21 December 2011 | 9:06 pm


Site-specific DOTA/europium-labeling of recombinant human relaxin-3 for receptor-ligand interaction studies

Abstract  
Relaxin-3 (also known as INSL7) is a recently identified neuropeptide belonging to the insulin/relaxin superfamily. It has putative roles in the regulation of stress responses, food intake, and reproduction by activation of its cognate G-protein-coupled receptor RXFP3. It also binds and activates the relaxin family peptide receptors RXFP1 and RXFP4 in vitro. To obtain a europium-labeled relaxin-3 as tracer for studying the interaction of these receptors with various ligands, in the present work we propose a novel site-specific labeling strategy for the recombinant human relaxin-3 that has been previously prepared in our laboratory. First, the N-terminal 6×His-tag of the single-chain relaxin-3 precursor was removed by Aeromonas aminopeptidase and all of the primary amines of the resultant peptide were reversibly blocked by citroconic anhydride. Second, the A-chain N-terminus of the blocked peptide was released by endoproteinase Asp-N cleavage that removed the linker peptide between the B- and A-chains. Third, an alkyne moiety was introduced to the newly released A-chain N-terminus by reaction with the highly active primary amine-specific N-hydroxysuccinimide ester. Fourth, after removal of the reversible blockage under mild acidic condition, europium-loaded DOTA with an azide moiety was introduced to the two-chain relaxin-3 carrying the alkyne moiety through click chemistry. Using this site-specific labeling strategy, homogeneous monoeuropium-labeled human relaxin-3 could be obtained with good overall yield. In contrast, conventional random labeling resulted in a complex mixture that was poorly resolved because human relaxin-3 has four primary amine moieties that all react with the modification reagent. Both saturation and competition binding assays demonstrated that the DOTA/Eu3+-labeled relaxin-3 retained high binding affinity for human RXFP3, RXFP4, and RXFP1 and was therefore a suitable non-radioactive and stable tracer to study the interaction of various natural or designed ligands with these receptors. Using this site-specific labeling strategy, other functional probes, such as fluorescent dyes, biotin, or nanoparticles could also be introduced to the A-chain N-terminal of the recombinant human relaxin-3. Additionally, we improved the time-resolved fluorescence assay for the DOTA-bound europium ion which paves the way for the use of DOTA as a lanthanide chelator for protein and peptide labeling in future studies.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-10
  • DOI 10.1007/s00726-011-1164-z
  • Authors
    • Wei-Jie Zhang, Institute of Protein Research, College of Life Sciences and Technology, Tongji University, Shanghai, 200092 China
    • Xiao Luo, Institute of Protein Research, College of Life Sciences and Technology, Tongji University, Shanghai, 200092 China
    • Ya-Li Liu, Central Laboratory, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120 China
    • Xiao-Xia Shao, Institute of Protein Research, College of Life Sciences and Technology, Tongji University, Shanghai, 200092 China
    • John D. Wade, Florey Neuroscience Institutes, The University of Melbourne, Victoria, 3010 Australia
    • Ross A. D. Bathgate, Florey Neuroscience Institutes, The University of Melbourne, Victoria, 3010 Australia
    • Zhan-Yun Guo, Institute of Protein Research, College of Life Sciences and Technology, Tongji University, Shanghai, 200092 China
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 20 December 2011 | 5:47 pm


Modulation of innate immune-related pathways in nicotine-treated SH-SY5Y cells

Abstract  
Although nicotine has a broad impact on both the central and peripheral nervous systems, the molecular mechanisms remain largely unknown, especially at the signaling pathway level. To investigate that aspect, we employed both conventional molecular techniques, such as quantitative real-time PCR and Western blotting analysis, and high-throughput microarray approach to identify the genes and signaling pathways that are modulated by nicotine. We found 14 pathways significantly altered in SH-SY5Y neuroblastoma cells. Of these, the Toll-like receptor pathway (TLR; p = 2.57 × 10?4) is one of the most important innate immune pathways. The death receptor pathway (DR; p = 8.71 × 10?4), whose transducers coordinate TLR signals and help conduct the host immune response to infection, was also significantly changed by nicotine. Furthermore, we found that several downstream pathways of TLR and DR signaling, such as PI3K/AKT signaling (p = 9.55 × 10?6), p38 signaling (p = 2.40 × 10?6), and ERK signaling (p = 1.70 × 10?4), were also significantly modulated by nicotine. Interestingly, most of the differentially expressed genes in these pathways leading to nuclear factor ?B (NF-?B) activation and those important inhibitors of pathways leading to apoptosis, including FLIP and Bcl-2, were up-regulated by nicotine. Taken together, our findings demonstrate that nicotine can regulate multiple innate immune-related pathways, and our data thus provide new clues to the molecular mechanisms underlying nicotine’s regulatory effects on neurons.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-13
  • DOI 10.1007/s00726-011-1171-0
  • Authors
    • Wen-Yan Cui, State Key Laboratory of Protein and Plant Gene Research, Peking University, 100871 Beijing, China
    • Ju Wang, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 1670 Discovery Drive, Suite 110, Charlottesville, VA 22911, USA
    • Jinxue Wei, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 1670 Discovery Drive, Suite 110, Charlottesville, VA 22911, USA
    • Junran Cao, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 1670 Discovery Drive, Suite 110, Charlottesville, VA 22911, USA
    • Sulie L. Chang, Department of Biology, Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ, USA
    • Jun Gu, State Key Laboratory of Protein and Plant Gene Research, Peking University, 100871 Beijing, China
    • Ming D. Li, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 1670 Discovery Drive, Suite 110, Charlottesville, VA 22911, USA
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 20 December 2011 | 5:47 pm


Detection of transglutaminase activity using click chemistry

Abstract  
Transglutaminase 2 (TG2) is a Ca2+-dependent enzyme able to catalyze the formation of ?(?-glutamyl)-lysine crosslinks between polypeptides, resulting in high molecular mass multimers. We have developed a bioorthogonal chemical method for the labeling of TG2 glutamine-donor proteins. As amine-donor substrates we used a set of azide- and alkyne-containing primary alkylamines that allow, after being crosslinked to glutamine-donor proteins, specific labeling of these proteins via the azide-alkyne cycloaddition. We demonstrate that these azide- and alkyne-functionalized TG2 substrates are cell permeable and suitable for specific labeling of TG2 glutamine-donor substrates in HeLa and Movas cells. Both the Cu(I)-catalyzed and strain promoted azide-alkyne cycloaddition proved applicable for subsequent derivatization of the TG2 substrate proteins with the desired probe. This new method for labeling TG2 substrate proteins introduces flexibility in the detection and/or purification of crosslinked proteins, allowing differential labeling of cellular proteins.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-13
  • DOI 10.1007/s00726-011-1198-2
  • Authors
    • Remon van Geel, Department of Biomolecular Chemistry, Nijmegen Centre for Molecular Life Sciences, Institute for Molecules and Materials and Netherlands Proteomics Centre, Radboud University, Nijmegen, The Netherlands
    • Marjoke F. Debets, Department of Bio-organic Chemistry, Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands
    • Dennis W. P. M. Löwik, Department of Bio-organic Chemistry, Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands
    • Ger J. M. Pruijn, Department of Biomolecular Chemistry, Nijmegen Centre for Molecular Life Sciences, Institute for Molecules and Materials and Netherlands Proteomics Centre, Radboud University, Nijmegen, The Netherlands
    • Wilbert C. Boelens, Department of Biomolecular Chemistry, Nijmegen Centre for Molecular Life Sciences, Institute for Molecules and Materials and Netherlands Proteomics Centre, Radboud University, Nijmegen, The Netherlands
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 16 December 2011 | 6:28 pm


Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide

Abstract  
The neonatal small intestine is susceptible to damage by endotoxin, but effective methods for prevention and treatment are lacking. N-acetylcysteine (NAC) is a widely used precursor of l-cysteine for animal cells and plays an important role in protecting cells against oxidative stress. This study was conducted with the lipopolysaccharide (LPS)-challenged piglet model to determine the effects of NAC on intestinal function. Eighteen piglets were randomly allocated into control, LPS and LPS + NAC groups. The control and LPS groups were fed a corn- and soybean meal-based diet, and the LPS + NAC group was fed the basal diet +500 mg/kg NAC. On days 10, 13 and 20 of the trial, the LPS and LPS + NAC groups received intraperitoneal administration of LPS (100 ?g/kg BW), whereas the control piglets received saline. On day 20 of the trial, d-xylose (0.1 g/kg BW) was orally administrated to all piglets 2 h after LPS or saline injection, and blood samples were collected 1 h thereafter. One hour blood xylose test was used to measure intestinal absorption capacity and mucosal integrity, and diamine oxidase (DAO) was used as a marker of intestinal injury. On day 21 of the trial, pigs were killed to obtain the intestinal mucosa. Compared to the control, LPS challenge reduced (P < 0.05) the concentrations of d-xylose (a marker of intestinal absorption) in plasma, activities of DAO in the jejunal mucosa, the ratio of villus height to crypt depth in the jejunal mucosa, RNA/DNA and protein/DNA in the jejunal and ileal mucosae, while increasing (P < 0.05) DAO activity in plasma and caspase-3 expression in the intestinal mucosa. The adverse effects of LPS were partially ameliorated (P < 0.05) by NAC supplementation. Moreover, NAC prevented the LPS-induced decrease in claudin-1 and occludin expression in the jejunal and ileal mucosae. Collectively, these results indicate that dietary NAC supplementation alleviates the mucosal damage and improves the absorptive function of the small intestine in LPS-challenged piglets.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-10
  • DOI 10.1007/s00726-011-1191-9
  • Authors
    • Yongqing Hou, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023 China
    • Lei Wang, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023 China
    • Wei Zhang, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023 China
    • Zhenguo Yang, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023 China
    • Binying Ding, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023 China
    • Huiling Zhu, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023 China
    • Yulan Liu, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023 China
    • Yinsheng Qiu, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023 China
    • Yulong Yin, Research Center for Healthy Breeding of Livestock and Poultry, Hunan Engineering and Research Center of Animal and Poultry Science and Key Laboratory for Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Hunan, 410125 China
    • Guoyao Wu, Department of Animal Science, Texas A & M University, College Station, TX 77843, USA
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 16 December 2011 | 6:28 pm


Role of the mu-opioid receptor in opioid modulation of immune function

Abstract  
Endogenous opioids are synthesized in vivo to modulate pain mechanisms and inflammatory pathways. Endogenous and exogenous opioids mediate analgesia in response to painful stimuli by binding to opioid receptors on neuronal cells. However, wide distribution of opioid receptors on tissues and organ systems outside the CNS, such as the cells of the immune system, indicate that opioids are capable of exerting additional effects in the periphery, such as immunomodulation. The increased prevalence of infections in opioid abuser-based epidemiological studies further highlights the immunosuppressive effects of opioids. In spite of their many debilitating side effects, prescription opioids remain a gold standard for treatment of chronic pain. Therefore, given the prevalence of opioid use and abuse, opioid-mediated immune suppression presents a serious concern in our society today. It is imperative to understand the mechanisms by which exogenous opioids modulate immune processes. In this review, we will discuss the role of opioid receptors and their ligands in mediating immune-suppressive functions. We will summarize recent studies on direct and indirect opioid modulation of the cells of the immune system, as well as the role of opioids in exacerbation of certain disease states.

  • Content Type Journal Article
  • Category Invited Review
  • Pages 1-16
  • DOI 10.1007/s00726-011-1163-0
  • Authors
    • Jana Ninkovi?, Department of Surgery, University of Minnesota, 420 Delaware St SE, MMC195, Minneapolis, MN 55455, USA
    • Sabita Roy, Division of Infection, Inflammation and Vascular Biology, Department of Surgery and Pharmacology, University of Minnesota, MMC 195, 420 Delaware Street SE, Minneapolis, MN 55455, USA
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 14 December 2011 | 5:42 pm


The influence of sex, age and heritability on human skeletal muscle carnosine content

Abstract  
The dipeptide carnosine is found in high concentrations in human skeletal muscle and shows large inter-individual differences. Sex and age are determining factors, however, systematic studies investigating the sex effects on muscle carnosine content throughout the human lifespan are lacking. Despite the large inter-individual variation, the intra-individual variation is limited. The question may be asked whether the carnosine content is a muscle characteristic which may be largely genetically determined. A total of 263 healthy male and female subjects of 9–83 years were divided into five different age groups: prepubertal children (PC), adolescents (A), young adults (YA), middle adults (MA) and elderly (E). We included 25 monozygotic and 22 dizygotic twin pairs among the entire study population to study the heritability. The carnosine content was measured non-invasively in the gastrocnemius medialis and soleus by proton magnetic resonance spectroscopy (1H-MRS). In boys, carnosine content was significantly higher (gastrocnemius 22.9%; soleus 44.6%) in A compared to PC, while it did not differ in girls. A decrease (~16%) was observed both in males and females from YA to MA. However, elderly did not have lower carnosine levels in comparison with MA. Higher correlations were found in monozygotic (r = 0.86) compared to dizygotic (r = 0.51) twins, in soleus muscle, but not in gastrocnemius. In conclusion, this study found an effect of puberty on muscle carnosine content in males, but not in females. Muscle carnosine decreased mainly during early adulthood and hardly from adulthood to elderly. High intra-twin correlations were observed, but muscle-dependent differences preclude clear conclusions toward heritability.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-8
  • DOI 10.1007/s00726-011-1197-3
  • Authors
    • Audrey Baguet, Department of Movement and Sport Sciences, Ghent University, Watersportlaan 2, 9000 Ghent, Belgium
    • Inge Everaert, Department of Movement and Sport Sciences, Ghent University, Watersportlaan 2, 9000 Ghent, Belgium
    • Erik Achten, Ghent Institute for Functional Magnetic Resonance (GifMI), Ghent University, Ghent, Belgium
    • Martine Thomis, Department of Biomedical Kinesiology, Research Center for Exercise and Health, FaBeR, K.U. Leuven, Leuven, Belgium
    • Wim Derave, Department of Movement and Sport Sciences, Ghent University, Watersportlaan 2, 9000 Ghent, Belgium
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 14 December 2011 | 5:42 pm


Synaptic localisation of agmatinase in rat cerebral cortex revealed by virtual pre-embedding

Abstract  
Light microscopic evidence suggested a synaptic role for agmatinase, an enzyme capable of inactivating the putative neurotransmitter and endogenous anti-depressant agmatine. Using electron microscopy and an alternative pre-embedding approach referred to as virtual pre-embedding, agmatinase was localised pre- and postsynaptically, to dendritic spines, spine and non-spine terminals, and dendritic profiles. In dendritic spines, labelling displayed a tendency towards the postsynaptic density. These results further strengthen a synaptic role for agmatine and strongly suggest a regulatory role for synaptically expressed agmatinase.

  • Content Type Journal Article
  • Category Short Communication
  • Pages 1-5
  • DOI 10.1007/s00726-011-1195-5
  • Authors
    • V. I. Madai, Institute for Integrative Neuroanatomy, Charité—Universitätsmedizin Berlin, Philippstr. 12, 10115 Berlin, Germany
    • W. C. Poller, Institute for Integrative Neuroanatomy, Charité—Universitätsmedizin Berlin, Philippstr. 12, 10115 Berlin, Germany
    • D. Peters, Institute for Integrative Neuroanatomy, Charité—Universitätsmedizin Berlin, Philippstr. 12, 10115 Berlin, Germany
    • J. Berger, Institute for Integrative Neuroanatomy, Charité—Universitätsmedizin Berlin, Philippstr. 12, 10115 Berlin, Germany
    • K. Paliege, Institute for Integrative Neuroanatomy, Charité—Universitätsmedizin Berlin, Philippstr. 12, 10115 Berlin, Germany
    • R. Bernard, Institute for Integrative Neuroanatomy, Charité—Universitätsmedizin Berlin, Philippstr. 12, 10115 Berlin, Germany
    • R. W. Veh, Institute for Integrative Neuroanatomy, Charité—Universitätsmedizin Berlin, Philippstr. 12, 10115 Berlin, Germany
    • G. Laube, Institute for Integrative Neuroanatomy, Charité—Universitätsmedizin Berlin, Philippstr. 12, 10115 Berlin, Germany
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 12 December 2011 | 6:12 pm


GABA is an effective immunomodulatory molecule

Abstract  
In recent years, it has become clear that there is an extensive cross-talk between the nervous and the immune system. Somewhat surprisingly, the immune cells themselves do express components of the neuronal neurotransmitters systems. What role the neurotransmitters, their ion channels, receptors and transporters have in immune function and regulation is an emerging field of study. Several recent studies have shown that the immune system is capable of synthesizing and releasing the classical neurotransmitter GABA (?-aminobutyric acid). GABA has a number of effects on the immune cells such as activation or suppression of cytokine secretion, modification of cell proliferation and GABA can even affect migration of the cells. The immune cells encounter GABA when released by the immune cells themselves or when the immune cells enter the brain. In addition, GABA can also be found in tissues like the lymph nodes, the islets of Langerhans and GABA is in high enough concentration in blood to activate, e.g., GABA-A channels. GABA appears to have a role in autoimmune diseases like multiple sclerosis, type 1 diabetes, and rheumatoid arthritis and may modulate the immune response to infections. In the near future, it will be important to work out what specific effects GABA has on the function of the different types of immune cells and determine the underlying mechanisms. In this review, we discuss some of the recent findings revealing the role of GABA as an immunomodulator.

  • Content Type Journal Article
  • Category Invited Review
  • Pages 1-8
  • DOI 10.1007/s00726-011-1193-7
  • Authors
    • Zhe Jin, Department of Neuroscience, Molecular Physiology and Neuroscience, Uppsala University, BMC, BOX 593, 75124 Uppsala, Sweden
    • Suresh Kumar Mendu, Department of Neuroscience, Molecular Physiology and Neuroscience, Uppsala University, BMC, BOX 593, 75124 Uppsala, Sweden
    • Bryndis Birnir, Department of Neuroscience, Molecular Physiology and Neuroscience, Uppsala University, BMC, BOX 593, 75124 Uppsala, Sweden
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 12 December 2011 | 6:12 pm


Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions

Abstract  
Transglutaminase 2 (TG2) is a multifunctional member of an enzyme family: it modifies glutamine residues by cross-linking proteins and incorporating primary amines into them, has protein disulphide isomerase and protein kinase activities, mediates trans-membrane signal transduction and interactions between cell surface proteins and the extracellular matrix. These unusual multiple roles encoded into one polypeptide chain suggest that genomic variations in the TGM2 gene should be limited. Indeed, the available information in databases shows that unlike in the case of most other transglutaminases there are no common single nucleotide polymorphisms in exons of human TGM2. We collected data on and produced some of the rare genetic variants of TGM2 by site directed mutagenesis and found that some were less stable than the most abundant (wild type) enzyme variant and the majority had deficient transamidating activity. Further studies are required to clarify the pathologic significance of these rare TGM2 alleles in the human population.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-11
  • DOI 10.1007/s00726-011-1194-6
  • Authors
    • Róbert Király, Department of Biochemistry and Molecular Biology, Apoptosis and Genomics Research Group of Hungarian Academy of Sciences, Medical and Health Science Center, University of Debrecen, Egyetem tér 1, Debrecen, 4012 Hungary
    • Endre Barta, Department of Biochemistry and Molecular Biology, Apoptosis and Genomics Research Group of Hungarian Academy of Sciences, Medical and Health Science Center, University of Debrecen, Egyetem tér 1, Debrecen, 4012 Hungary
    • László Fésüs, Department of Biochemistry and Molecular Biology, Apoptosis and Genomics Research Group of Hungarian Academy of Sciences, Medical and Health Science Center, University of Debrecen, Egyetem tér 1, Debrecen, 4012 Hungary
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 12 December 2011 | 6:12 pm


Plant aminoaldehyde dehydrogenases oxidize a wide range of nitrogenous heterocyclic aldehydes

Abstract  
The metabolic degradation of aldehydes is catalyzed by oxidoreductases from which aldehyde dehydrogenases (EC 1.2.1) comprise nonspecific or substrate-specific enzymes. The latter subset is represented, e.g., by NAD+-dependent aminoaldehyde dehydrogenases (AMADHs; EC 1.2.1.19) oxidizing a group of naturally occurring ?-aminoaldehydes including polyamine oxidation products. Recombinant isoenzymes from pea (PsAMADH1 and 2) and tomato (LeAMADH1 and 2) were subjected to kinetic measurements with synthetic aldehydes containing a nitrogenous heterocycle such as pyridinecarbaldehydes and their halogenated derivatives, (pyridinylmethylamino)-aldehydes, pyridinyl propanals and aldehydes derived from purine, 7-deazapurine and pyrimidine to characterize their substrate specificity and significance of the resulting data for in vivo reactions. The enzymatic production of the corresponding carboxylic acids was analyzed by liquid chromatography coupled to electrospray ionization mass spectrometry. Although the studied AMADHs are largely homologous and supposed to have a very similar active site architecture, significant differences were observed. LeAMADH1 displayed the broadest specificity oxidizing almost all compounds followed by PsAMADH2 and 1. In contrast, LeAMADH2 accepted only a few compounds as substrates. Pyridinyl propanals were converted by all isoenzymes, usually better than pyridinecarbaldehydes and aldehydes with fused rings. The K m values for the best substrates were in the range of 10?5–10?4 M. Nevertheless, the catalytic efficiency values (V max/K m) reached only a very small fraction of that with 3-aminopropanal (except for LeAMADH1 activity with two pyridine-derived compounds). Docking experiments using the crystal structure of PsAMADH2 were involved to discuss differences in results with position isomers or alkyl chain homologs.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-14
  • DOI 10.1007/s00726-011-1174-x
  • Authors
    • Jan Frömmel, Department of Protein Biochemistry and Proteomics, Centre of the Region Haná for Biotechnological and Agricultural Research, Faculty of Science, Palacký University, Šlechtitel? 11, 783 71 Olomouc, Czech Republic
    • Miroslav Soural, Department of Organic Chemistry, Faculty of Science, Palacký University, 17. listopadu 12, 771 46 Olomouc, Czech Republic
    • Martina Tylichová, Department of Protein Biochemistry and Proteomics, Centre of the Region Haná for Biotechnological and Agricultural Research, Faculty of Science, Palacký University, Šlechtitel? 11, 783 71 Olomouc, Czech Republic
    • David Kope?ný, Department of Protein Biochemistry and Proteomics, Centre of the Region Haná for Biotechnological and Agricultural Research, Faculty of Science, Palacký University, Šlechtitel? 11, 783 71 Olomouc, Czech Republic
    • Gabriel Demo, Central European Institute of Technology and Department of Biochemistry, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
    • Michaela Wimmerová, Central European Institute of Technology and Department of Biochemistry, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
    • Marek Šebela, Department of Protein Biochemistry and Proteomics, Centre of the Region Haná for Biotechnological and Agricultural Research, Faculty of Science, Palacký University, Šlechtitel? 11, 783 71 Olomouc, Czech Republic
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 12 December 2011 | 6:12 pm


Homocysteine enhances clot-promoting activity of endothelial cells via phosphatidylserine externalization and microparticles formation

Abstract  
Total elevated plasma homocysteine (Hcy) is a risk factor for thromboembolism. Vascular endothelium is important to regulate coagulation, but the impact of Hcy on the clot-promoting activity (CPA) of endothelial cells has not been fully understood. In our study, human umbilical vein endothelial cells (HUVECs) were treated with Hcy (8, 20, 80, 200, 800 ?mol/L) for 24 h. Annexin V was utilized to detect phosphatidylserine (PS) externalization and endothelial microparticles (MPs) formation. CPA was assessed by recalcification time and purified clotting complex tests. We found that Hcy enhanced the externalized PS and consequent CPA of HUVECs in a dose-dependent fashion, effect of Hcy had statistical significance at 800 ?mol/L. In addition, Hcy also increased the shedding of procoagulant endothelial MPs. Blocking of PS with 128 nmol/L annexin V reduced approximately 70% CPA of HUVECs and endothelial MPs, but human anti-tissue factor antibody had little inhibitive effect. Our results showed that Hcy increased CPA of HUVECs via PS externalization and MPs release. Our present study has implications for hyperhomocysteinemia-related hypercoagulability.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-8
  • DOI 10.1007/s00726-011-1196-4
  • Authors
    • Jiuxin Zhu, Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, 150081 China
    • Rui Xie, Health Ministry Key Laboratory of Cell Transplantation, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, 150001 China
    • Xianmei Piao, Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, 150081 China
    • Yunlong Hou, Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, 150081 China
    • Chongbao Zhao, Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, 150081 China
    • Guofen Qiao, Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, 150081 China
    • Baofeng Yang, Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, 150081 China
    • Jialan Shi, Health Ministry Key Laboratory of Cell Transplantation, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, 150001 China
    • Yanjie Lu, Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, 150081 China
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 12 December 2011 | 6:12 pm


Relationship between protein folding kinetics and amino acid properties

Abstract  
The successful prediction of protein-folding rates based on the sequence-predicted secondary structure suggests that the folding rates might be predicted from sequence alone. To pursue this question, we directly predict the folding rates from amino acid sequences, which do not require any information on secondary or tertiary structure. Our work achieves 88% correlation with folding rates determined experimentally for proteins of all folding types and peptide, suggesting that almost all of the information needed to specify a protein’s folding kinetics and mechanism is comprised within its amino acid sequence. The influence of residue on folding rate is related to amino acid properties. Hydrophobic character of amino acids may be an important determinant of folding kinetics, whereas other properties, size, flexibility, polarity and isoelectric point, of amino acids have contributed little to the folding rate constant.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-6
  • DOI 10.1007/s00726-011-1189-3
  • Authors
    • Jitao T. Huang, State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, 300071 China
    • Dajie J. Xing, State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, 300071 China
    • Wei Huang, State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, 300071 China
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 12 December 2011 | 6:12 pm


Effects of leucine and citrulline versus non-essential amino acids on muscle protein synthesis in fasted rat: a common activation pathway?

Abstract  
Leucine (LEU) is recognized as a major regulator of muscle protein synthesis (MPS). Citrulline (CIT) is emerging as a potent new regulator. The aim of our study was to compare MPS modulation by CIT and LEU in food-deprived rats and to determine whether their action was driven by similar mechanisms. Rats were either freely fed (F, n = 10) or food deprived for 18 h. Food-deprived rats were randomly assigned to one of four groups and received per os, i.e., gavage, saline (S, n = 10), l-leucine (1.35 g/kg, LEU, n = 10), l-citrulline (1.80 g/kg CIT, n = 10) or isonitrogenous non-essential amino acids (NEAA, n = 10). After gavage, the rats were injected with a flooding dose of [13C] valine to determine MPS. The rats were killed 50 min after the injection of the flooding dose. Blood was collected for amino acid, glucose and insulin determinations. Tibialis anterior muscles were excised for determination of MPS and for Western blot analyses of the PI3K/Akt, mTORC1, ERK1/2/MAPK pathways and AMP kinase component. MPS was depressed by 61% in starved rats (Saline vs. Fed, P < 0.05). Administration of amino acids (NEAA, LEU or CIT) completely abolished this decrease (NEAA, CIT, LEU vs. Fed, NS). Food deprivation affected the phosphorylation status of the mTORC1 pathway and AMP kinase (Saline vs. Fed, P < 0.05). LEU and CIT administration differently stimulated the mTORC1 pathway (LEU > CIT). LEU but not CIT increased the phosphorylation of rpS6 at serine 235/236. Our findings clearly demonstrated that both CIT and LEU were able to stimulate MPS, but this effect was likely related to the nitrogen load. LEU, CIT and NEAA may have different actions on MPS in this model as they share different mTORC1 regulation capacities.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-8
  • DOI 10.1007/s00726-011-1172-z
  • Authors
    • Servane Le Plénier, Département Biologie Expérimentale, Métabolique et Clinique, EA 4466, Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    • Stéphane Walrand, Unité de Nutrition Humaine, UMR 1019, INRA/UdA, CNRH, Auvergne, Clermont-Ferrand, France
    • Richard Noirt, Département Biologie Expérimentale, Métabolique et Clinique, EA 4466, Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    • Luc Cynober, Département Biologie Expérimentale, Métabolique et Clinique, EA 4466, Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    • Christophe Moinard, Département Biologie Expérimentale, Métabolique et Clinique, EA 4466, Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 12 December 2011 | 6:12 pm


Recent advances in the development of tissue transglutaminase (TG2) inhibitors

Abstract  
Tissue transglutaminase (TG2) is a Ca2+-dependent enzyme and probably the most ubiquitously expressed member of the mammalian transglutaminase family. TG2 plays a number of important roles in a variety of biological processes. Via its transamidating function, it is responsible for the cross-linking of proteins by forming isopeptide bonds between glutamine and lysine residues. Intracellularly, Ca2+ activation of the enzyme is normally tightly regulated by the binding of GTP. However, upregulated levels of TG2 are associated with many disease states like celiac sprue, certain types of cancer, fibrosis, cystic fibrosis, multiple sclerosis, Alzheimer’s, Huntington’s and Parkinson’s disease. Selective inhibitors for TG2 both cell penetrating and non-cell penetrating would therefore serve as novel therapeutic tools for the treatment of these disease states. Moreover, they would provide useful tools to fully elucidate the cellular mechanisms TG2 is involved in and help comprehend how the enzyme is regulated at the cellular level. The current paper is intended to give an update on the recently discovered classes of TG2 inhibitors along with their structure–activity relationships. The biological properties of these derivatives, in terms of both activity and selectivity, will also be reported in order to translate their potential for future therapeutic developments.

  • Content Type Journal Article
  • Category Invited Review
  • Pages 1-9
  • DOI 10.1007/s00726-011-1188-4
  • Authors
    • E. Badarau, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK
    • R. J. Collighan, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK
    • M. Griffin, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 12 December 2011 | 6:12 pm


Adrenergic modulation of immune cells: an update

Abstract  
Sympathoadrenergic pathways are crucial to the communication between the nervous system and the immune system. The present review addresses emerging issues in the adrenergic modulation of immune cells, including: the specific pattern of adrenoceptor expression on immune cells and their role and changes upon cell differentiation and activation; the production and utilization of noradrenaline and adrenaline by immune cells themselves; the dysregulation of adrenergic immune mechanisms in disease and their potential as novel therapeutic targets. A wide array of sympathoadrenergic therapeutics is currently used for non-immune indications, and could represent an attractive source of non-conventional immunomodulating agents.

  • Content Type Journal Article
  • Category Invited Review
  • Pages 1-17
  • DOI 10.1007/s00726-011-1186-6
  • Authors
    • Franca Marino, Department of Clinical Medicine, Section of Experimental and Clinical Pharmacology, University of Insubria, Via Ottorino Rossi n. 9, 21100 Varese, VA, Italy
    • Marco Cosentino, Department of Clinical Medicine, Section of Experimental and Clinical Pharmacology, University of Insubria, Via Ottorino Rossi n. 9, 21100 Varese, VA, Italy
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 7 December 2011 | 5:43 pm


Modulating protein activity and cellular function by methionine residue oxidation

Abstract  
The sulfur-containing amino acid residue methionine (Met) in a peptide/protein is readily oxidized to methionine sulfoxide [Met(O)] by reactive oxygen species both in vitro and in vivo. Methionine residue oxidation by oxidants is found in an accumulating number of important proteins. Met sulfoxidation activates calcium/calmodulin-dependent protein kinase II and the large conductance calcium-activated potassium channels, delays inactivation of the Shaker potassium channel ShC/B and L-type voltage-dependent calcium channels. Sulfoxidation at critical Met residues inhibits fibrillation of atherosclerosis-related apolipoproteins and multiple neurodegenerative disease-related proteins, such as amyloid beta, ?-synuclein, prion, and others. Methionine residue oxidation is also correlated with marked changes in cellular activities. Controlled key methionine residue oxidation may be used as an oxi-genetics tool to dissect specific protein function in situ.

  • Content Type Journal Article
  • Category Review Article
  • Pages 1-13
  • DOI 10.1007/s00726-011-1175-9
  • Authors
    • Zong Jie Cui, Institute of Cell Biology, Beijing Normal University, Beijing, 100875 China
    • Zong Qiang Han, Institute of Cell Biology, Beijing Normal University, Beijing, 100875 China
    • Zhi Ying Li, Institute of Cell Biology, Beijing Normal University, Beijing, 100875 China
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 6 December 2011 | 6:04 pm


Beta-alanine (Carnosyn™) supplementation in elderly subjects (60–80 years): effects on muscle carnosine content and physical capacity

Abstract  
The aim of this study was to investigate the effects of beta-alanine supplementation on exercise capacity and the muscle carnosine content in elderly subjects. Eighteen healthy elderly subjects (60–80 years, 10 female and 4 male) were randomly assigned to receive either beta-alanine (BA, n = 12) or placebo (PL, n = 6) for 12 weeks. The BA group received 3.2 g of beta-alanine per day (2 × 800 mg sustained-release Carnosyn™ tablets, given 2 times per day). The PL group received 2 × (2 × 800 mg) of a matched placebo. At baseline (PRE) and after 12 weeks (POST-12) of supplementation, assessments were made of the muscle carnosine content, anaerobic exercise capacity, muscle function, quality of life, physical activity and food intake. A significant increase in the muscle carnosine content of the gastrocnemius muscle was shown in the BA group (+85.4%) when compared with the PL group (+7.2%) (p = 0.004; ES: 1.21). The time-to-exhaustion in the constant-load submaximal test (i.e., TLIM) was significantly improved (p = 0.05; ES: 1.71) in the BA group (+36.5%) versus the PL group (+8.6%). Similarly, time-to-exhaustion in the incremental test was also significantly increased (p = 0.04; ES 1.03) following beta-alanine supplementation (+12.2%) when compared with placebo (+0.1%). Significant positive correlations were also shown between the relative change in the muscle carnosine content and the relative change in the time-to-exhaustion in the TLIM test (r = 0.62; p = 0.01) and in the incremental test (r = 0.48; p = 0.02). In summary, the current data indicate for the first time, that beta-alanine supplementation is effective in increasing the muscle carnosine content in healthy elderly subjects, with subsequent improvement in their exercise capacity.

  • Content Type Journal Article
  • Category Original Article
  • Pages 1-8
  • DOI 10.1007/s00726-011-1190-x
  • Authors
    • Serena del Favero, School of Physical Education and Sport, University of Sao Paulo, Av Mello de Moraes, 65, Butantã, Sao Paulo, SP 05508-030, Brazil
    • Hamilton Roschel, School of Physical Education and Sport, University of Sao Paulo, Av Mello de Moraes, 65, Butantã, Sao Paulo, SP 05508-030, Brazil
    • Marina Y. Solis, School of Physical Education and Sport, University of Sao Paulo, Av Mello de Moraes, 65, Butantã, Sao Paulo, SP 05508-030, Brazil
    • Ana P. Hayashi, School of Physical Education and Sport, University of Sao Paulo, Av Mello de Moraes, 65, Butantã, Sao Paulo, SP 05508-030, Brazil
    • Guilherme G. Artioli, School of Physical Education and Sport, University of Sao Paulo, Av Mello de Moraes, 65, Butantã, Sao Paulo, SP 05508-030, Brazil
    • Maria Concepción Otaduy, Division of Radiology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
    • Fabiana B. Benatti, School of Physical Education and Sport, University of Sao Paulo, Av Mello de Moraes, 65, Butantã, Sao Paulo, SP 05508-030, Brazil
    • Roger C. Harris, Junipa Ltd, Newmarket, Suffolk, UK
    • John A. Wise, Natural Alternatives International Inc, San Marcos, USA
    • Cláudia C. Leite, Division of Radiology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
    • Rosa M. Pereira, Division of Rheumatology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
    • Ana L. de Sá-Pinto, Division of Rheumatology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
    • Antonio Herbert Lancha-Junior, School of Physical Education and Sport, University of Sao Paulo, Av Mello de Moraes, 65, Butantã, Sao Paulo, SP 05508-030, Brazil
    • Bruno Gualano, School of Physical Education and Sport, University of Sao Paulo, Av Mello de Moraes, 65, Butantã, Sao Paulo, SP 05508-030, Brazil
    • Journal Amino Acids
    • Online ISSN 1438-2199
    • Print ISSN 0939-4451

Posted on 5 December 2011 | 6:34 pm







Sonstige Hinweise:



Chemie-Fanshop

 Seiteninfo:


 
Die Urheberrechte sowie die Verantwortung fuer den Inhalt der verlinkten Artikel hat der in der Quelle genannte Anbieter.
 
Sie möchten Ihre überwiegend mit fachlichen Inhalten zur Chemie, Biochemie etc. ausgestattete Internetseite hier aufgeführt sehen: eMail genügt! Nach Prüfung des Inhalts Ihrer Chemieseite entscheiden wir über eine eventuelle Aufnahme (kostenlos, ohne Bedingungen). Für einfache Einträge nutzen Sie bitte das Registrierungsformular!
Verlinkung:
http://www.internetchemie.info/rss/aminosaeuren.php
Stichworte:
Chronologische Liste mit Fachartikeln zum Thema Chemie, Aminosäuren, Amino Acids.
Stand:
25.04.2011


Internetchemie ChemLin © 1996 - 2011 A. J.


Add to Google Internetchemie bei WebNews Infos zum Internetchemie RSS News Feed