The poly(ADP-ribose) glycohydrolase inhibitor gallotannin blocks oxidative astrocyte death.
Poly(ADP-ribose) polymerase (PARP) is now recognized as an important mediator of cell death, but a role for poly(ADP-ribose) glycohydrolase (PARG) in cell death has not previously been described. PARG is the key enzyme degrading ADP-ribose polymers produced by PARP. Here we report effects of the PARG inhibitor gallotannin on oxidative cell death. Pre-incubation of cultured murine astrocytes with as little as 100 nM gallotannin produced significant reductions in H2O2-induced cell death assessed both 24 and 72 h after H2O2 exposure. Gallotannin was more than 10-fold more potent than the PARP inhibitor benzamide in preventing H2O2-induced cell death. These results provide the first evidence that PARG inhibitors could be used to prevent oxidative cell death.
Ying
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Department of Neurology, University of California, Veterans Affairs Medical Center, San Francisco 94121, USA.
Swanson
R A
RA
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000201:enzymology; D001549:Benzamides / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006861:Hydrogen Peroxide / Q000378:metabolism; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects
D001549:Benzamides; D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; C037689:benzamide; D006861:Hydrogen Peroxide; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase