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The poly(ADPribose) glycohydrolase inhibitor gallotannin blocks oxidative astrocyte death

Ying, Weihai; Swanson, Raymond A.

Neuroreport:
Neuropharmacology
Abstract

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.

Author Information

1 Department of Neurology (127), University of California, Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA

2 Corresponding Author: Raymond A. Swanson

Acknowledgements: We thank Vannita Simma for expert technical assistance. This work was supported by NIH P50 NS 14543 and by the Department of Veterans Affairs.

Received 24 January 2000; accepted 17 February 2000

© 2000 Wolters Kluwer Health | Lippincott Williams & Wilkins