H2O2 accelerates cellular senescence by accumulation of acetylated p53 via decrease in the function of SIRT1 by NAD+ depletion.
作者： Ayako Furukawa , Saeko Tada-Oikawa , Shosuke Kawanishi , Shinji Oikawa
DOI: 10.1159/000104152
关键词:
摘要: It has been reported that p53 acetylation, which promotes cellular senescence, can be regulated by the NAD(+)-dependent deacetylase SIRT1, human homolog of yeast Sir2, a protein modulates lifespan. To clarify role SIRT1 in senescence induced oxidative stress, we treated normal diploid fibroblast TIG-3 cells with H(2)O(2) and examined DNA cleavage, depletion intracellular NAD(+), expression p21, acetylated p53, cell cycle arrest, senescence-associated beta-galactosidase (SA-beta-gal) activity. cleavage was observed immediately H(2)O(2), though no death observed. NAD(+) levels were also decreased significantly. Pre-incubation poly (ADP-ribose) polymerase (PARP) inhibitor resulted preservation levels. The amount increased at 4h after treatment, while there little to decrease expression. level p21 12h continued increase for up 24h. Additionally, exposure arrest 24h SA-beta-gal activity 48h. This pathway likely plays an important acceleration stress.
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