H sub(2)O sub(2)-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 of 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 H sub(2)O sub(2)-induced cell death in A172 cells, a human glioma cell line. H sub(2)O sub(2) induced a dose- and time-dependent cell death. The cell death was prevented by thiols (dithiothreitol and glutathione), iron chelators (deferoxamine and phenanthroline), H sub(2)O sub(2) scavengers (catalase and pyruvate), and a hydroxyl radical scavenger (dimethylthiourea). Antioxidants N,N'-diphenyl-p-phenylenediamine (DPPD) and Trolox had no effect on the H sub(2)O sub(2)-induced cell death. Lipid peroxidation did not increase in human glioma cells exposed to H sub(2)O sub(2). The PARP inhibitor 3-aminobenzamide prevented the cell death induced by H sub(2)O sub(2). The PARP activity was increased by H sub(2)O sub(2) and the H sub(2)O sub(2) effect was prevented by 3-aminobenzamide, dithiothreitol, and phenanthroline. The ATP depletion induced by H sub(2)O sub(2) was prevented by catalase, dithiothreitol, phenanthroline, and 3-aminobenzamide, but not by DPPD. These results indicate that the H sub(2)O sub(2)-induced cell death is mediated by PARP activation but not by lipid peroxidation in human glioma cells.