TY - JOUR
T1 - 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
AU - Endres, Matthias
AU - Scott, Gwen S.
AU - Salzman, Andrew L.
AU - Kun, Ernest
AU - Moskowitz, Michael A.
AU - Szabó, Csaba
N1 - Funding Information:
This work was supported by Massachusetts General Hospital Interdepartmental Stroke Project Grants from the National Institutes of Health (NS10828) to M.A.M., the Deutsche Forschungsgemeinschaft (En343/1-1) to M.E., and the Octamer Research Foundation (Mill Valley, CA, USA) and the Spinal Cord Research Foundation to G.S., and the National Institutes of Health (RO1HL59266) to C.S.
PY - 1998/6/26
Y1 - 1998/6/26
N2 - 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.
AB - 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.
KW - Glia
KW - Inflammation
KW - Nitric oxide (NO)
KW - Reperfusion
KW - Superoxide
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U2 - 10.1016/S0014-2999(98)00381-1
DO - 10.1016/S0014-2999(98)00381-1
M3 - Article
C2 - 9721031
AN - SCOPUS:0031856719
SN - 0014-2999
VL - 351
SP - 377
EP - 382
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 3
ER -