title: Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion.
abstract: Apoptotic and necrotic cell death are well characterized and are influenced by intracellular ATP levels. Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated by DNA strand breaks, physiologically participates in DNA repair. Overactivation of PARP after cellular insults can lead to cell death caused by depletion of the enzyme's substrate beta-nicotinamide adenine dinucleotide and of ATP. In this study, we have differentially elicited apoptosis or necrosis in mouse fibroblasts. Fibroblasts from PARP-deficient (PARP(-/-)) mice are protected from necrotic cell death and ATP depletion but not from apoptotic death. These findings, together with cell death patterns in PARP(-/-) animals receiving other types of insults, indicate that PARP activation is an active trigger of necrosis, whereas other mechanisms mediate apoptosis.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: H C
authors.initials: HC
authors.lastname: Ha
authors.forename: S H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D004789:Enzyme Activation; D007424:Intracellular Fluid / Q000378:metabolism; D008769:Methylnitronitrosoguanidine / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D019014:fas Receptor; D008769:Methylnitronitrosoguanidine; D000255:Adenosine Triphosphate; D011065:Poly(ADP-ribose) Polymerases