Role of the peroxynitrite-poly (ADP-ribose) polymerase pathway in the pathogenesis of liver injury.
Oxidative and nitrosative stress triggers DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP). One of the key triggers of DNA single strand breakage in pathophysiological conditions is peroxynitrite, a reactive species produced from the reaction of nitric oxide and superoxide. Activation of PARP can dramatically lower the intracellular concentration of its substrate, nicotinamide adenine dinucleotide, thus slowing the rate of glycolysis, electron transport and subsequently ATP formation. This process can result in cell dysfunction and cell death. Here we review the role of PARP in various forms of liver injury.
Gero
Domokos
D
Department of Human Physiology and Clinical Experimental Research, Semmelweis University Medical School, Budapest, Hungary.
Szabó
Csaba
C
D000818:Animals; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008107:Liver Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D030421:Peroxynitrous Acid; D011065:Poly(ADP-ribose) Polymerases