Poly(ADP-ribose) polymerase-1 dependence of stress-induced transcription factors and associated gene expression in glia.
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.
Ha
Hyo Chol
HC
Department of Neuroscience and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Hester
Lynda D
LD
Snyder
Solomon H
SH
D000818:Animals; D002384:Catalysis; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D050981:Erythroid-Specific DNA-Binding Factors; D005260:Female; D005786:Gene Expression Regulation; D051863:Host Cell Factor C1; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008934:Mitogens / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D050811:Octamer Transcription Factor-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D050794:STAT1 Transcription Factor; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013312:Stress, Physiological; D015534:Trans-Activators / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D016207:Cytokines; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1; D008070:Lipopolysaccharides; D008934:Mitogens; D016328:NF-kappa B; D050811:Octamer Transcription Factor-1; C494166:Pou2f1 protein, mouse; D050794:STAT1 Transcription Factor; D016329:Sp1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D011065:Poly(ADP-ribose) Polymerases