H2O2-induced cell death in human glioma cells: Role of lipid peroxidation and PARP activation

Reactive oxygen species (ROS) have been implicated in the pathogenesis of a number of neurodegenerative disorders. However, the underlying mechanism o f ROS-induced cell injury remains to be defined. This study was undertaken to examine the role of lipid peroxidation and poly (ADP-ribose),polymerase (PARP) activation in H2O2-induced cell death in A172 cells, a human glioma cell line, H2O2 induced a dose- and time-dependent cell death. The cell dea th was prevented by thiols (dithiothreitol and glutathione), iron chelators (deferoxamine and phenanthroline), H2O2 scavengers (catalase and pyruvate) , and a hydroxyl radical scavenger (dimethylthiourea). Antioxidants N,N'-di phenyl-p-phenylenediamine (DPPD) and Trolox had no effect on the H2O2-induc ed cell death. Lipid peroxidation did not increase in human glioma cells ex posed to H2O2. The PARP inhibitor 3-aminobenzamide prevented the cell death induced by H2O2. The PARP activity was increased by H2O2 and the H2O2 effe ct was prevented by 3-aminobenzamide, dithiothreitol, and phenanthroline. T he ATP depletion induced by H2O2 was prevented by catalase, dithiothreitol, phenanthroline, and 3-aminobenzamide, but not by DPPD. These results indic ate that the H2O2-induced cell death is mediated by PARP activation but not by lipid peroxidation in human glioma cells.