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Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.22, #4)
Editorial (pp. V-V).
are pleased to announce a new service for our authors and readers: Online First, the immediate online publication of all accepted papers as soon as the authors have returned the corrected proofs. Whereas the fully electronic versions of Amino Acids used to appear at the same time as the print journal, from now on the electronic version of all articles will be available to subscribers via the Internet weeks before the printed version appears. This means an enormous reduction in publication time. It will no longer be necessary for manuscripts to wait until the “next available issue”.As each paper is ready for publication, it will be published on the Web with its own publication date as follows: “Published online: 〈date when placed on Springer's LINK server〉”. Each article will receive an international identification code – the “Digital Object Identifier” (DOI), which is registered with the International DOI Foundation and is unique, like the ISBN for books or the ISSN for periodicals. Contributions published Online First are citable by journal title and DOI. The print version will also have the final page numbers, the DOI and the online publication date. Furthermore, the DOI is linked to the URL (Uniform Resource Locator) and the bibliography when the printed issue is released. The DOI is never changed and can be used, for example, to create hyperlinks between Online First articles. Online First articles appear in their final form. Therefore, papers cannot be changed or withdrawn after electronic publication. Any corrections that might be necessary have to be made in an Erratum, which will be hyperlinked to the article.Each article will be announced in LINK alert, which is a free alerting service (http://link.springer.de/alert). A table of contents showing all papers that have been accepted for publication in Amino Acids but not yet printed can be found via the Springer Web page:http://link.springer.de/link/service/journals/00726/tocs.htm orhttp://link.springer-ny.com/link/service/journals/00726/tocs.htmby clicking Online First. The Editors-in-Chief and Springer-Verlag
Peptoid inhibition of trypanothione reductase as a potential antitrypanosomal and antileishmanial drug lead by C. Chan; H. Yin; J. H. McKie; A. H. Fairlamb; K. T. Douglas (pp. 297-308).
One route to the design of lead compounds for rational drug design approaches to developing drugs against trypanosomiasis, Chagas' disease and leishmaniasis is to develop novel inhibitors of the parasite-specific enzyme trypanothione reductase. A lead inhibitor based on a peptoid structure was designed in the present study based on the known strong competitive inhibition of trypanothione reductase by N-benzoyl-Leu-Arg-Arg-β-naphthylamide and N-benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-β-naphthylamide. In the target peptoid the arginyl residues were replaced by alkylimidazolium units and the benzyloxycarbonyl group by the benzylaminocarbonyl function. The peptoid was synthesised using t-butoxycarbonyl protection chemistry and couplings were activated by 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate. The resulting peptoid was shown to be a competitive inhibitor of recombinant trypanothione reductase from Trypanosoma cruzi with a Ki value of 179 μM and with only weak inhibition of human erythrocyte glutathione reductase (the inhibition of glutathione reductase was at least 291-fold weaker than of trypanothione reductase).
Keywords: Keywords: Drug leads; Glutathione; Antiparasitics; Enzyme inhibitors; Rational drug design
The cytoprotective role of taurine in exercise-induced muscle injury by R. Dawson, Jr.; M. Biasetti; S. Messina; J. Dominy (pp. 309-324).
Intense exercise is thought to increase oxidative stress and damage muscle tissue. Taurine is present in high concentration in skeletal muscle and may play a role in cellular defenses against free radical-mediated damage. The aim of this study was to determine if manipulating muscle levels of taurine would alter markers of free radical damage after exercise-induced injury. Adult male Sprague-Dawley rats were supplemented via the drinking water with either 3% (w/v) taurine (n = 10) or the competitive taurine transport inhibitor, β-alanine (n = 10), for one month. Controls (n = 20) drank tap water containing 0.02% taurine and all rats were placed on a taurine free diet. All the rats except one group of sedentary controls (n = 10) were subjected to 90 minutes of downhill treadmill running. Markers of cellular injury and free radical damage were determined along with tissue amino acid content. The 3% taurine treatment raised plasma levels about 2-fold and 3% β-alanine reduced plasma taurine levels about 50%. Taurine supplementation (TS) significantly increased plasma glutamate levels in exercised rats. Exercise reduced plasma methionine levels and taurine prevented its decline. Taurine supplementation increased muscle taurine content significantly in all muscles except the soleus. β-alanine decreased muscle taurine content about 50% in all the muscles examined. Lipid peroxidation (TBARS) was significantly increased by exercise in the extensor digitorium longus (EDL) and gastrocnemius (GAST) muscles. Both taurine and β-alanine completely blocked the increase in TBARs in the EDL, but had no effect in the GAST. Muscle content of the cytosolic enzyme, lactate dehydrogenase (LDH) was significantly decreased by exercise in the GAST muscle and this effect was attenuated by both taurine and β-alanine. Muscle myeloperoxidase (MPO) activity was significantly elevated in the gastrocnemius muscle, but diet had no effect. MPO activity was significantly increased by exercise in the liver and both taurine and β-alanine blocked this effect. There was no effect of either exercise or the diets on MPO activity in the lung or spleen. Running performance as assessed by a subjective rating scale was improved by taurine supplementation and there was a significant loss in body weight in the β-alanine-treated rats 24 hours after exercise. In summary, taurine supplementation or taurine depletion had measurable cytoprotective actions to attenuate exercise-induced injury.
Keywords: Keywords: Taurine; β-Alanine; Exercise; Oxidative stress; Muscle injury
Asymmetric hydrogenation of dehydrodipeptides bearing different protecting groups by Chr. Döbler; H.-J. Kreuzfeld; Chr. Fischer; M. Michalik (pp. 325-331).
N-[(Z)-N-Benzoyl- or N-boc-(2-fluorophenyl)dehydroalanyl]-(R)- or (S)-phenyl-alanines 1,2,5 and 6 were hydrogenated in the presence of chiral and achiral rhodium complexes. The optical induction is compared to the results obtained using the corresponding esters as substrates.
Keywords: Keywords: Dehydrodipeptides; Non-proteinogenic dipeptides; Chiral rhodium catalysts; Diastereoselectivity; Asymmetric hydrogenation
Downregulation of taurine uptake in multidrug resistant Ehrlich ascites tumor cells by K. A. Poulsen; T. Litman; J. Eriksen; J. Mollerup; I. H. Lambert (pp. 333-350).
In daunorubicin resistant Ehrlich ascites tumor cells (DNR), the initial taurine uptake was reduced by 56% as compared to the parental, drug sensitive Ehrlich cells. Kinetic experiments indicated that taurine uptake in Ehrlich cells occurs via both high- and low-affinity transporters. The maximal rate constant for the initial taurine uptake was reduced by 45% (high-affinity system) and 49% (low affinity system) in the resistant subline whereas the affinity of the transporters to taurine was unchanged. By immunoblotting we identified 3 TauT protein bands in the 50–70 kDa region. A visible reduction in the intensity of the band with the lowest molecular weight was observed in resistant cells. Quantitative RT-PCR indicated a significant reduction in the amount of taurine transporter mRNA in the resistant cells. Drug resistance in DNR Ehrlich cells is associated with overexpression of the mdr1 gene product P-glycoprotein (P-gp). Using 5 progressively DNR resistant Ehrlich cell sublines with different P-gp expression pattern no correlation between taurine uptake and P-gp expression was found. Taurine uptake in MDR1 transfected NIH/3T3 mouse fibroblasts was in contrast to the findings in Ehrlich cells increased compared to the parental fibroblasts. It is concluded that the reduced taurine uptake in resistant Ehrlich cells reflects a down regulation of the taurine transporter at the mRNA and protein level and it is most probably not related to P-gp overexpression.
Keywords: Keywords: Amino acids; P-glycoprotein; TauT; NIH/3T3; Daunorubicin
Effects of sulfur containing amino acids on iron and nitric oxide stimulated catecholamine oxidation by M. Biasetti; R. Dawson Jr. (pp. 351-368).
Taurine is a free amino acid found in high concentrations in tissues containing catecholamines. The ability of taurine and its metabolic precursors to inhibit or stimulate catecholamine oxidation and subsequent quinone formation was examined. Ferric chloride was used as the catalyzing agent to stimulate L-dopa or norepinephrine oxidation and NO donors were also examined for their actions to stimulate quinone formation. Taurine attenuated iron-stimulated quinone formation from catecholamines suggesting that it may function as an endogenous antioxidant. Several other sulfur-containing amino acids (homocysteic acid, cysteine sulfinic acid and SAM) were found to inhibit catecholamine oxidation. Among other amino acids tested, homocysteine had biphasic effects; attenuating L-dopa oxidation catalyzed by ferric chloride and potentiating norepinephrine's oxidation catalyzed by both ferric chloride and sodium nitroprusside (SNP). Homotaurine and homocysteine (1 or 10 mM) greatly stimulated SNP-induced norepinephrine oxidation. Homotaurine potentiated quinone formation in the presence of ferric iron and this effect was attenuated by desferroxamine. In order to exclude a possible NO/iron interaction in SNP's oxidizing action, SIN-1 chloride, a specific NO-donor, was tested as an oxidizing agent. The failure of desferroxamine or taurine to attenuate SIN-1 oxidation of norepinephrine suggests that peroxynitrite-mediated oxidation was likely the dominant mechanism. Our results show that endogenous sulfur containing amino acids, like taurine, could serve a protective role to reduce cellular damage associated with both NO and metal-stimulated catecholamine oxidation.
Keywords: Keywords: Amino acids; Taurine; Catecholamines; Ferric chloride; Nitric oxide; Homocysteine; Homotaurine
Effects of bilobalide on amino acid release and electrophysiology of cortical slices by F. A. Jones; S. S. Chatterjee; J. A. Davies (pp. 369-379).
This study investigated the effects of bilobalide, a constituent of Ginkgo biloba, on potassium and veratridine-induced release of glutamate and aspartate from mouse cortical slices. We also studied its effects on spontaneous and N-methyl-D-aspartate (NMDA)-induced depolarizations elicited in magnesium-free artificial cerebrospinal fluid (aCSF) as well as its effect on NO-711 (a γ-aminobutyric acid (GABA) uptake inhibitor)-induced depolarizations. Bilobalide, 100 μM significantly reduced both glutamate and aspartate release elicited by potassium or veratridine. Bilobalide (5–100 μM) also significantly reduced the frequency of NO-711 induced depolarizations, however, it had no effect on spontaneous or on NMDA-induced depolarizations at 5–200 μM. These results suggest that the neuroactive properties of bilobalide may be mediated by a reduction in excitatory amino acid neurotransmitter release.
Keywords: Keywords: Amino acids; Bilobalide; Mouse cortical slices; Glutamate; Depolarizations
Regulation of the rate of synthesis of nitric oxide by Mg2+ and hypoxia. Studies in rat heart mitochondria by S. Manzo-Ávalos; V. Pérez-Vázquez; J. Ramírez; L. Aguilera-Aguirre; J. C. González-Hernández; M. Clemente-Guerrero; R. Villalobos-Molina; A. Saavedra-Molina (pp. 381-389).
In isolated rat heart mitochondria, L-arginine is oxidized by a nitric oxide synthase (mtNOS) achieving maximal rates at 1 mM L-arginine. The NOS inhibitor NG-nitro-L-arginine methyl ester (NAME) inhibits the increase in NO production. Extramitochondrial free magnesium inhibited NOS production by 59% at 3.2 mM. The mitochondrial free Mg2+ concentration increased to different extents in the presence of L-arginine (29%), the NO donor (S-nitroso-N-acetylpenicillamine) (105%) or the NOS inhibitors L-NAME (48%) or NG-nitro-L-arginine methyl ester, NG-monomethyl-L-arginine (L-NMMA) (53%). Under hypoxic conditions, mtNOS activity was inhibited by Mg2+ by up to 50% after 30 min of incubation. Reoxygenation restored the activity of the mtNOS to pre-hypoxia levels. The results suggest that in heart mitochondria there is an interaction between Mg2+ levels and mtNOS activity which in turn is modified by hypoxia and reoxygenation.
Keywords: Keywords: Amino acids; Nitric oxide; Free magnesium; Hypoxia-reoxygenation; L-Arginine; Heart mitochondria
The role of taurine added to pulmonary reperfusion solutions in isolated guinea pig lungs by E. Öz; M. C. Sivrikoz; V. Halit; A. Altunkaya; G. Take (pp. 391-403).
An experimental comparative study on isolated guinea pig-lungs has been undertaken to determine the probable beneficial effects of adding taurine to pulmonary reperfusion solutions in lung ischemia-reperfusion. 20 guinea pigs were used. The isolated lungs (n = 10 in each group) previously being perfused by oxygenated Krebs-Henseleit solution were put in normothermic ischemic conditions. After 3 hours of normothermic ischemia the lungs were reperfused (with Krebs-Henseleit solution in the control group, Krebs-Henseleit solution plus taurine 10−2 M in the experiment group) for 20 minutes. Pulmonary artery pressures, tissue malondialdehyde (MDA) and glutathione (GSH) levels were measured before and after the ischemic period and also at the end of reperfusion. Malondialdehyde and glutathione levels of the pefusate were measured before ischemic period and at the end of reperfusion. An electron microscopic analysis was performed on the lung tissues before and after the ischemic period and also at the end of reperfusion. Decreased pulmonary artery pressure, tissue perfusate MDA levels and increased perfusate GSH levels were observed in taurine added group. Electron microscopic evaluation supported our findings indicating preservation of lamellar bodies of type II pneumocytes. It is concluded that taurine may play an important role in protecting tissue against ischemia-reperfusion injury by functioning as an antioxidant.
Keywords: Keywords: Amino acids; Lung; Ischemia-reperfusion injury; Taurine
Effect of Ca2+ and Mg2+ on the Mn-superoxide dismutase from rat liver and heart mitochondria by V. Pérez-Vázquez; J. Ramírez; L. Aguilera-Aguirre; J. C. González-Hernández; M. Clemente-Guerrero; S. Manzo-Ávalos; S. Uribe; A. Saavedra-Molina (pp. 405-416).
The manganese superoxide dismutase (Mn-SOD) converts superoxide anions to hydrogen peroxide plus oxygen, providing the first line of defense against oxidative stress in mitochondria. Heart mitochondria exhibited higher Mn-SOD activity than liver mitochondria. In mitochondria from both tissues Mn-SOD activity decreased after incubation at low oxygen concentration (hypoxic mitochondria). The effects of free Ca2+ ([Ca2+]f) and free Mg2+ ([Mg2+]f) on normoxic and hypoxic mitochondria from either organ were tested. In normoxic mitochondria from either tissue, both [Ca2+]f and [Mg2+]f activated the enzyme, although [Mg2+]f was less efficient as an activator and the effect was lower in heart than in liver mitochondria. When added simultaneously, high [Ca2+]f and [Mg2+]f exhibited additive effects which were more pronounced in heart mitochondria and were observed regardless of whether mitochondria had been incubated under normal or low oxygen. The data suggest that [Ca2+]f plays a role in regulating Mn-SOD in concert with the activation of aerobic metabolism.
Keywords: Keywords: Amino acids; Liver mitochondria; Heart mitochondria; Mn-SOD; Calcium; Magnesium; Superoxide anion
The protective effect of taurine pretreatment on carbon tetrachloride-induced hepatic damage – A light and electron microscopic study by S. Dinçer; S. Özenirler; E. Öz; G. Akyol; C. Özoğul (pp. 417-426).
The results regarding taurine pretreatment on CCl4-induced hepatic injury are controversial. To assess the therapeutic efficacy of taurine on rat liver injury, hepatic malondialdehyde, glutathione, and hydroxyproline levels together with morphologic alterations in the liver following CCl4 administration were investigated. The rats were divided into three groups. Taurine-treated animals received 15 ml/kg/day of a 5% taurine solution by a gastric tube for 5 days before administering CCl4 (2 ml/kg, intraperitoneally, in a single dose). CCl4-treated rats received the same amount of saline solution. Control animals received no treatment. The increase of hepatic malondialdehyde formation in the CCl4-treated group was partially prevented by taurine pretreatment, but taurine had no significant effect on the glutathione and hydroxyproline content in the CCl4-treated rats. Taurine pretreatment induced a marked beneficial effect regarding the prevention of hepatocellular necrosis and atrophy as demonstrated morphologically. In conclusion, these results suggest that taurine pretreatment might not significantly change the biochemical parameters, but prevents the morphologic damage caused by CCl4 in the early stages.
Keywords: Keywords: Taurine; Liver; Carbon tetrachloride; Malondialdehyde; Glutathione; Hydroxyproline; Amino acids; Light and electron microscopy
Thin layer chromatographical detection of tyrosine produced from l-[U-14C]phenylalanine by ruminal microbes by R. I. Khan; R. Onodera; M. R. Amin (pp. 427-432).
Thin layer chromatographical detection of tyrosine (Tyr) synthesized from l-[U-14C]phenylalanine (Phe) (1 mM) by rumen bacteria (B) and protozoa (P) collected from fistulated Japanese Goat was carried out. About 16 and 12% of the added Phe was converted to Tyr by B and P, respectively. Large amount of radioactivity in ether fractions indicated an abundant production of aromatic acids from Phe. Small amount of radioactivity found in CO2 fractions implied an occurrence of considerable decarboxylation reaction(s) by rumen bacteria and protozoa.
Keywords: Keywords: Amino acids; Tyrosine; Phenylalanine; Rumen bacteria; Protozoa