Ha Hyo Chol, Hester Lynda D, Snyder Solomon H
Department of Neuroscience and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3270-5. doi: 10.1073/pnas.052712399. Epub 2002 Feb 19.
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.
聚(ADP-核糖)聚合酶-1(PARP-1,EC )是一种由DNA链断裂激活的核酶,在生理上参与DNA修复。细胞损伤导致PARP-1过度激活会耗尽其底物β-烟酰胺腺嘌呤二核苷酸和ATP,从而导致细胞死亡。PARP-1缺陷(PARP-1-/-)小鼠对多种形式的炎症具有保护作用。在本研究中,我们发现在PARP-1-/-神经胶质细胞中,几种应激激活的转录因子缺失,同时细胞因子和细胞黏附分子的基因表达降低。我们还表明,其中一些基因的表达增加与PARP-1催化活性无关。这些发现表明,PARP-1通过调节炎症相关基因的转录在初始炎症反应中起关键作用。