title: Effects of homocysteine on apoptosis-related proteins and anti-oxidant systems in isolated human lymphocytes.
abstract: 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 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. 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 single-stranded 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 enhanced oxidative stress.
authors.affiliation: Laboratory of Functional Neurochemistry, Neurological Institute C. Mondino, Pavia, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Mangiagalli
authors.forename: Alberta
authors.initials: A
authors.lastname: Samuele
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Armentero
authors.forename: Eleonora
authors.initials: E
authors.lastname: Bazzini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nappi
authors.forename: Fabio
authors.initials: F
authors.lastname: Blandini
mesh_terms: D000328:Adult; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000097:blood; D006710:Homocysteine / Q000097:blood / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood; D013482:Superoxide Dismutase / Q000097:blood
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D006710:Homocysteine; D013482:Superoxide Dismutase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases