Role of nitrosative stress and poly(ADP-ribose) polymerase activation in myocardial reperfusion injury.
Ischemia and reperfusion injury leads to a complex pathophysiological process, which in turn results in the generation of free radicals. Peroxynitrite, a highly reactive species causes DNA single strand breaks, which activates the nuclear enzyme, poly (ADP-ribose) polymerase (PARP). The activation of PARP leads to an energy consuming inefficient repair cycle with subsequent depletion of NAD(+) and ATP pools and necrotic cell death. The present review overviews the pathophysiological role of the peroxynitrite-PARP pathway in cardiac ischemia/reperfusion injury with special reference to the therapeutic potential of PARP inhibitors in the treatment of this disease.
Szabó
Gábor
G
Department of Cardiac Surgery, University of Heidelberg, Germany. dzsi@hotmail.com
Bährle
Susanne
S
D000818:Animals; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D030421:Peroxynitrous Acid / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism*
D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D026361:Reactive Nitrogen Species; D030421:Peroxynitrous Acid; D011065:Poly(ADP-ribose) Polymerases