TAILIEUCHUNG - Báo cáo khoa học: Effects of homocysteine on apoptosis-related proteins and anti-oxidant systems in isolated human lymphocytes

Homocysteine (Hcy) is anonprotein-forming sulphur amino acid that plays an important role in remethylation and trans-sulphuration processes. In recent years, it has been suggested that increased levels of plasma Hcy may play a role in the pathogenesis of various diseases, particularly at the cardiovascular level. The pathogenic mechanism of hyperhomocysteinemia, however, has not been clarified. Because oxygen radicals can be generated by the auto-oxidation of this amino acid, it has been suggested that Hcy may cause cellular damage through oxidative mechanisms, ultimately leading to apoptotic cell death. . | Eur. J. Biochem. 271 1671-1676 2004 FEBS 2004 doi Effects of homocysteine on apoptosis-related proteins and anti-oxidant systems in isolated human lymphocytes Anna Manaiaaalli1 Alberta Samuele1 Marie-Therese Armentero1. Eleonora Bazzini1 Giusenne Nanni1 2 BB M B B B M wV M wV M B B B B B B F w B B B B B B B B B B B B B B Bl B B B BB B B B B Bf B BB Bb B B Bf B BB BB B Bl B B B BM B w B BB BB BB BB B w BB BB BB B and Fabio Blandini1 1 Laboratory of Functional Neurochemistry Neurological Institute C. Mondino Pavia Italy 2 Department of Neurology and Otorhinolaryngology University La Sapienza Rome Italy Homocysteine Hcy is a nonprotein-forming sulphur amino acid that plays an important role in remethylation and trans-sulphuration processes. In recent years it has been suggested that increased levels of plasma Hcy may play a role in the pathogenesis of various diseases particularly at the cardiovascular level. The pathogenic mechanism of hyperhomocysteinemia however has not been clarified. Because oxygen radicals can be generated by the autooxidation of this amino acid it has been suggested that Hcy may cause cellular damage through oxidative mechanisms ultimately leading to apoptotic cell death. In this study we sought to investigate the effects of Hcy on oxidative damage and antioxidant agent levels as well as on apoptosis-related proteins and apoptosis occurrence in human cells. For this purpose we measured levels of Bcl-2 caspase-3 and caspase-9 activity Cu Zn superoxide dismutase reduced glutathione lipid peroxidation malondialdehyde and 4-hydroxy-2 E -nonenal concentrations apoptotic singlestranded DNA and nuclear changes in human isolated lymphocytes exposed to increasing concentrations of Hcy. Incubation with Hcy did not induce significant changes in any of these biomarkers. Therefore our results do not support the existence of a direct link between increased levels of Hcy and the occurrence of a pro-apoptotic state mediated by

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