10Th International Congress on Amino Acids and Proteins (ICAAP)
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Amino Acids (2007) 33: I–LXX DOI 10.1007/s00726-007-0578-0 Printed in The Netherlands 10th International Congress on Amino Acids and Proteins (ICAAP) Kallithea, Greece August 20–25, 2007 Abstracts Presidents: M. Liakopoulou-Kyriakides, Aristotle University, Greece R. Harris, University of Chichester, U.K. K. C. Chou, Gordon Life Science Institute, U.S.A. Honorary President: G. Lubec, University of Vienna, Austria II Contents Amino Acids Metabolism – Diseases . III Amino Acids Racemization . V Bioinformatics and Biomedical. VIII Biotechnology – Enzyme Technology – Food Science . XII Drug Design. XIV Metabotropic Glutamate . XVII Neurobiology . XVIII Plant Amino Acids . XXXIV Polyamines – Transglutaminases. XXXVIII Proteins – Analysis . XLV Sports Exercise and Health . LII Synthesis Amino Acids – Medicinal Chemistry . LXII Transport . LXVIII 10th International Congress on Amino Acids and Proteins (ICAAP) Amino Acids Metabolism – Diseases Homocysteine and methylated arginines – novel Using male Wistar rats two separate studies were performed in which endogenous factors of the chronic musculoskeletal pain? the effect of glutamine on leucine oxidation, protein synthesis and pro- teolysis was estimated. At in vivo study, alanyl-glutamine or saline so- I. G. Bondarenko and J. Chydenius lution were infused to endotoxemic, whole body irradiated, or intact Nutritional=Clinical Biochemistry CHYDENIUS Clinic, Helsinki, (control) rats. At in vitro study, M. soleus and M. extensor digitorum Finland longus were incubated in medium containing 0, 500 or 2000 mmol Recurrent character of chronic musculoskeletal pain suggests that glutamine=L. The parameters of protein metabolism and leucine oxida- 14 there are endogenous chemical mediators sustaining local aseptic inflam- tion were measured using L-[1- C]leucine and=or according to the mation in the connective tissue involved. We propose that homocysteine rates of tyrosine release. Statistical comparisons were performed using (HCys) and methylated arginines – NG,NG-asymmetrical dimethylargi- ANOVA, Bonferroni test, and Student’s t-test. nine (ADMA) and N-monomethylarginine (N-MMA) – are not only Infusion of glutamine (alone or as alanyl-glutamine) induced a de- endogenous damaging factors to the cardiovascular system but also act crease in plasma BCAA levels, in leucine oxidation and an improvement as destabilisers of collagen and elastin in the joint cartilage, capsules, of protein balance related to the decrease in proteolysis both in intact, ligaments, and intramuscular connective tissue stroma. This, in turn, may endotoxemic and irradiated rats. In an in vitro study, supplementation of result in their mechanical weakness, recurrent structural imbalance, and, incubation media with glutamine in concentration of 2000 mmol=l de- therefore, facilitate pain. creased leucine oxidation by isolated muscles. With a qualitative standardised muscle test (a non-invasive diagnostic It is concluded that there are at least two mechanisms by which procedure accepted in functional neurology) for the excess of HCys, glutamine administration may affect protein metabolism in stress illness. ADMA and MMA in the tissues, we have examined 110 randomly se- The first is related to inhibitory effect of glutamine on production of lected out-patients (men: 30, women: 80, age: 40–68) with chronic recur- proinflammatory cytokines, the second is related to its effect on metabo- rent lower back=neck=joint pain of various origin. HCys was detected lism of BCAA. It is supposed that a negative feedback exists between elevated in 23 patients (20.9%), ADMA – in 76 (69.1%), N-MMA – in GLN level and BCAA oxidation in muscle which by unknown mecha- 11 (10%). Specific nutritional supplementation protocols designed for nism affects proteolysis. GLN administration can block this feedback the activation of the hydrolysis of HCys, ADMA, and N-MMA in the mechanism, decrease BCAA catabolism and improve protein balance. tissues, were introduced and have resulted in a substantial decrement of the intensity of pain and the frequency of its recurrence (within one year of follow-up). Beneficial effects of the nutritional supplementation were registered in all patients with the elevation of HCys, in 70 of 76 – with Is heme oxygenase-1 relevant to the anti-inflammatory the elevation of ADMA, and in 10 of 11 – with N-MMA elevation. activity of taurine chloramine? Mechanisms of destructive effects of HCys, ADMA, and N-MMA on B. Muz1, E. Kontny1, J. Marcinkiewicz2, and W. Mas´lin´ski1 connective tissue proteins and of the amending action of specific nutri- 1 Institute of Rheumatology, Warsaw, Poland tional compositions are being discussed. 2 Jagiellonian University, Cracow, Poland Fibroblast-like synoviocytes (FLS) are engaged in chronic synovitis and joint destruction, characteristic for rheumatoid arthritis (RA). We have Glutamine, branched-chain amino acids and protein previously reported that taurine chloramine (Tau-Cl) normalizes pathogenic metabolism functions of RA FLS by: (i) diminishing transcription factors (NFkB, AP-l) M. Holecˇek, T. Muthny´, M. Kovarˇ´ık, R. Sˇafra´nek, activities, (ii) down-regulation of pro-inflammatory gene transcription and L. Sˇisˇpera (IL-6, IL-8, COX-2, VEGF), and (iii) triggering growth arrest. Heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, has also been Department of Physiology, Charles University School of Medicine, reported to exert potent anti-inflammatory effects in vitro and to restrict Hradec Kra´love´, Czech Republic inflammation-associated tissue injury. Presently we have observed that Several studies have reported improvements in clinical outcome and in similar to hemin (25–100 mM), a known potent inducer of HO-l expression, nitrogen balance when glutamine (Gln) itself or Gln-containing peptides also Tau-Cl treatment (300–400 mM) up-regulates expression of HO-1 in were given to critically ill patients. However, the mechanism by which RA FLS at both mRNA and protein levels. Therefore, we ask the question Gln administration affects protein balance is not clear. Because of a tight whether in these cells HO-1 activity mediates anti-inflammatory effect of metabolic relationships between glutamine and branched-chain amino Tau-Cl. We have found that hemin inhibits both IL-1b-triggered production acids (BCAAs; valine, isoleucine and leucine), it can be hypothesised of pro-inflammatory cytokines (IL-6, IL-8) by RA FLS and PDGF-trig- that favourable effect of glutamine administration on protein metabolism gercd proliferation of these cells with potency similar to Tau-Cl. However, is related to its effect on BCAAs. pretreatment of the cells with HO-1 inhibitor (Zinc(II) Deuteroporphyrin IV 10th International Congress on Amino Acids and Proteins 1X-2,4-bisethyleneglycol – ZnDP) reverses only cytokine secretion but has ture where it is processed within the basolateral complex and relayed to no effect on either intracellular cytokine content or cell proliferation. These the central nucleus where an appropriate anxious=fear output is imple- observations suggest that either HO-1 activity is irrelevant to these RA FLS mented. The intercalated paracapsular islands and main intercalated responses or that in our system ZnDP is not effective enough to inhibit island, clusters of dopamine D1-rich GABAergic cells, seem to control activity of this enzyme. Thus, further studies are required to answer this the impulse trafficking between the two nuclei. Several lines of evidence question. On the other hand, in synovial fluid of RA patients we have found indicate that within the amygdala, GABA and glutamate, respectively very high (763 Æ 87 ng=ml) concentration of ferritin, a by-product of have an overall anxiolytic and anxiogenic role and that a number of other HO-1. Ferritin is an iron-binding protein, reported to possess anti-oxidant neurotransmitters interact with them to modulate anxiety. Experimental properties. We observed that upon either hemin or Tau-Cl treatment RA evidence from our laboratories is presented which suggests that dopa- FTS express only low intracellular level of ferritin light (FTL) and heavy mine and glutamate activate, via WT and VT, dopamine D1 and meta- (FTH) chains, Thus, RA FLS are not the major source of ferritin in botropic glutamate 5 receptors (mGluR5) located in the rostral and dorsal rheumatoid joints. Moreover, neither exogenously added FTL nor FTH amygdala and facilitate an anxiogenic output from the central nucleus. affected RA FLS responses (proliferation, cytokine synthesis). It is there- Immunocytochemical evidence is also provided which indicates that fore likely, that the other product of HO-l activity (e.g. CO) is probably CCK terminal=CCK2 matches and mismatches exist in the intercalated more relevant in regulating RA-FLS metabolism. In contrast, both FTL and cell masses and the basolateral complex respectively. These observations FTH prolonged in vitro survival of leukocytes isolated from rheumatoid suggest the CCK-2 receptor mediated CCK transmission operates both synovial fluid, suggesting that ferritin may support chronic inflammation. via WT and VT in the amygdala. CCK-4 and CCK-8S microinjected into the rostral amygdala produce an anxiogenic profile indicating that CCK transmission participates in anxiety. Our studies indicate that WT and VT Creatine supplementation modulates arginine metabolism signals specifically glutamate, dopamine and CCK-peptides become in- in alcoholic rats tegrated in the intercalated islands illustrating their role as a major node J. Nikolic, T.