Protective effects of 5-iodo-6-amino-1,2-benzopyrone, an inhibitor of poly(ADP-ribose) synthetase against peroxynitrite-induced glial damage and stroke development

Matthias Endres, Gwen S. Scott, Andrew L. Salzman, Ernest Kun, Michael A. Moskowitz, Csaba Szabó

    Research output: Contribution to journalArticle

    47 Scopus citations

    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 languageEnglish (US)
    Pages (from-to)377-382
    Number of pages6
    JournalEuropean Journal of Pharmacology
    Volume351
    Issue number3
    DOIs
    StatePublished - Jun 26 1998

    Keywords

    • Glia
    • Inflammation
    • Nitric oxide (NO)
    • Reperfusion
    • Superoxide

    ASJC Scopus subject areas

    • Pharmacology

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