Abstract
Peroxynitrite triggers DNA single-strand breakage, which activates the nuclear enzyme poly(ADP-ribose) synthetase (PARS). Activation of PARS depletes its substrate, NAD+, slowing the rate of glycolysis, electron transport, and ATP formation, resulting in cell necrosis. Here, we demonstrate that inhibition of PARS with the novel, potent PARS inhibitor 5-iodo-6-amino-1,2-benzopyrone (INH2BP) protects against peroxynitrite-induced cell death (as measured by measurement of mitochondrial respiration and release of lactate dehydrogenase) in C6 glioma cells in vitro, and in a murine stroke model in vivo. Inhibition of PARS with INH2BP may represent a novel approach for the experimental therapy of stroke. Copyright (C) 1998 Elsevier Science B.V. All rights reserved.
Original language | English (US) |
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Pages (from-to) | 377-382 |
Number of pages | 6 |
Journal | European Journal of Pharmacology |
Volume | 351 |
Issue number | 3 |
DOIs | |
State | Published - Jun 26 1998 |
Externally published | Yes |
Keywords
- Glia
- Inflammation
- Nitric oxide (NO)
- Reperfusion
- Superoxide
ASJC Scopus subject areas
- Pharmacology