The poly(ADP-ribose) glycohydrolase inhibitor gallotannin blocks oxidativeastrocyte death

Poly(ADP-ribose) polymerase (PARP) is now recognized as an important mediat or of cell death, but a role for poly(ADP-ribose) glycohydrolase (PARG) in fell death has not previously been described. PARG is the key enzyme degrad ing ADP-ribose polymers produced by PARP. Here we report effects of the PAR G inhibitor gallotannin on oxidative cell death. Preincubation 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 inhi bitor benzamide in preventing H2O2-induced cell death. These results provid e the first evidence that PARG inhibitors could be used to prevent oxidativ e cell death. NeuroReport 11:1385-1388 (C) 2000 Lippincott Williams & Wilki ns.