European Journal of Pharmacology 1998-06-26

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.

M Endres, G S Scott, A L Salzman, E Kun, M A Moskowitz, C Szabó

Index: Eur. J. Pharmacol. 351(3) , 377-82, (1998)

Full Text: HTML

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.

Related Compounds

  • INH2BP

Related Articles:

The Protective Effect of INH2BP, a Novel PARP Inhibitor 5-Iodo-6-Amino-1,2-Benzopyrone, Against Hydrogen Peroxide-Induced Apoptosis Through ERK and p38 MAPK in H9c2 Cells.

2015-01-01

[Pharmacology 96 , 259-70, (2015)]

4-Hydroxynonenal induces apoptosis in human osteoarthritic chondrocytes: the protective role of glutathione-S-transferase.

2008-01-01

[Arthritis. Res. Ther. 10 , R107, (2008)]

Dichloroacetate enhances apoptotic cell death via oxidative damage and attenuates lactate production in metformin-treated breast cancer cells.

2014-10-01

[Breast Cancer Res. Treat. 147(3) , 539-50, (2014)]

Inhibition of poly (ADP-ribose) synthetase by gene disruption or inhibition with 5-iodo-6-amino-1,2-benzopyrone protects mice from multiple-low-dose-streptozotocin-induced diabetes.

2001-07-01

[Br. J. Pharmacol. 133(6) , 909-19, (2001)]

Protection against peroxynitrite-induced fibroblast injury and arthritis development by inhibition of poly(ADP-ribose) synthase.

1998-03-31

[Proc. Natl. Acad. Sci. U. S. A. 95(7) , 3867-72, (1998)]

More Articles...