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Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3270-5. Epub 2002 Feb 19.

Poly(ADP-ribose) polymerase-1 dependence of stress-induced transcription factors and associated gene expression in glia.

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  • 1Department of Neuroscience and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1, EC ), a nuclear enzyme activated by DNA strand breaks, physiologically participates in DNA repair. Excessive activation of PARP-1 by cellular insults depletes its substrate beta-nicotinamide adenine dinucleotide and ATP, leading to cell death. PARP-1-deficient (PARP-1-/-) mice are protected from several forms of inflammation. In the present study, we demonstrate in PARP-1-/- glial cells a loss of several stress-activated transcription factors as well as decreased expression of genes for cytokines and cellular adhesion molecules. We also show that augmented expression of some of these genes is independent of PARP-1 catalytic activity. These findings indicate that PARP-1 plays a pivotal role in the initial inflammatory response by modulating transcription of inflammation-linked genes.

PMID:
11854472
PMCID:
PMC122508
DOI:
10.1073/pnas.052712399
[PubMed - indexed for MEDLINE]
Free PMC Article
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