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 Szabo

Research output: Contribution to journalArticle

47 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Poly Adenosine Diphosphate Ribose
Peroxynitrous Acid
Ligases
Neuroglia
Stroke
Investigational Therapies
Glycolysis
Electron Transport
L-Lactate Dehydrogenase
Glioma
NAD
Respiration
Cell Death
Necrosis
Adenosine Triphosphate
5-iodo-6-amino-1,2-benzopyrone
DNA
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

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

In: European Journal of Pharmacology, Vol. 351, No. 3, 26.06.1998, p. 377-382.

Research output: Contribution to journalArticle

Endres, Matthias ; Scott, Gwen S. ; Salzman, Andrew L. ; Kun, Ernest ; Moskowitz, Michael A. ; Szabo, Csaba. / 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. In: European Journal of Pharmacology. 1998 ; Vol. 351, No. 3. pp. 377-382.
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