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 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 H2O2-induced cell death in A172 cells, a human glioma cell line. H2O2 induced a dose- and time-dependent cell death. The cell death 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'-diphenyl-p-phenylenediamine (DPPD) and Trolox had no effect on the H2O2-induced cell death. Lipid peroxidation did not increase in human glioma cells exposed to H2O2. The PARP inhibitor 3-aminobenzamide prevented the cell death induced by H2O2. The PARP activity was increased by H2O2 and the H2O2 effect was prevented by 3-aminobenzamide, dithiothreitol, and phenanthroline. The ATP depletion induced by H2O2 was prevented by catalase, dithiothreitol, phenanthroline, and 3-aminobenzamide, but not by DPPD. These results indicate that the H2O2-induced cell death is mediated by PARP activation but not by lipid peroxidation in human glioma cells.
Lee
Y W
YW
Department of Neurosurgery, College of Medicine, Pusan National University, Korea.
Ha
M S
MS
Kim
Y K
YK
D001549:Benzamides / Q000494:pharmacology; D001932:Brain Neoplasms / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects*; D004229:Dithiothreitol / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005910:Glioma / Q000473:pathology*; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical; D015227:Lipid Peroxidation / Q000187:drug effects*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D001549:Benzamides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D017665:Hydroxyl Radical; C025160:3-aminobenzamide; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases; D005978:Glutathione; D004229:Dithiothreitol