Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion

Chol Ha Hyo Chol Ha, S. H. Snyder

Research output: Contribution to journalArticle

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 β-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.

Original languageEnglish (US)
Pages (from-to)13978-13982
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number24
DOIs
StatePublished - Nov 23 1999

ASJC Scopus subject areas

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