期刊
JOURNAL OF NEUROCHEMISTRY
卷 134, 期 4, 页码 668-676出版社
WILEY-BLACKWELL
DOI: 10.1111/jnc.13172
关键词
H3K9-ac; H3K9-me3; p53; resveratrol; SIRT1
资金
- National Natural Science Foundation of China (NSFC) [81371410, 81171205]
- National Basic Research Program of China (973 Program) [2011CB707506]
- Shanghai Pujiang Program [11PJD019]
- Biomedical Multidisciplinary Program of Shanghai Jiao Tong University [YG2014MS31]
- National Natural Science Foundation of China [81202811]
- China Postdoctoral Science Foundation [2014M550250]
- Shanghai Municipal Health Bureau Fund [20124320]
- National Parkinson Foundation
The protein deacetylase SIRT1 has been recognized to exert its protective effect by directly deacetylasing histone and many other transcriptional factors including p53. However, the effect of SIRT1 on p53 expression at the transcriptional level still remains to be elucidated. In this study, we found that rotenone treatment decreased cell viability, induced apoptosis, reduced SIRT1 level, and promoted p53 expression. Pre-treatment with resveratrol, a SIRT1 activator, could attenuate rotenone-induced cell injury and p53 expression, whereas down-regulation of SIRT1 directly increased p53 expression. Moreover, chromatin immunoprecipitation experiments showed that SIRT1 bound to H3K9 within the p53 promoter region, and this binding resulted in decreased H3K9 acetylation and increased H3K9 tri-methylation, thereby inhibiting p53 gene transcription. In conclusion, our data indicate that rotenone promotes p53 transcription and apoptosis through targeting SIRT1 and H3K9. This leads to nigrostriatal degeneration, the main pathogenic mechanism of motor features of Parkinson's disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据