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Rotenone affects p53 transcriptional activity and apoptosis via targeting SIRT 1 and H3K9 acetylation in SH ‐ SY 5Y cells
Author(s) -
Feng Ya,
Liu Te,
Dong SuYan,
Guo YanJie,
Jankovic Joseph,
Xu Huaxi,
Wu YunCheng
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13172
Subject(s) - rotenone , sirtuin 1 , neuroprotection , resveratrol , neurodegeneration , histone deacetylase , acetylation , chromatin immunoprecipitation , microbiology and biotechnology , chemistry , biology , transcription factor , histone , cancer research , gene expression , promoter , biochemistry , downregulation and upregulation , pharmacology , mitochondrion , gene , medicine , disease
The protein deacetylase SIRT 1 has been recognized to exert its protective effect by directly deacetylasing histone and many other transcriptional factors including p53. However, the effect of SIRT 1 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 SIRT 1 level, and promoted p53 expression. Pre‐treatment with resveratrol, a SIRT 1 activator, could attenuate rotenone‐induced cell injury and p53 expression, whereas down‐regulation of SIRT 1 directly increased p53 expression. Moreover, chromatin immunoprecipitation experiments showed that SIRT 1 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 SIRT 1 and H3K9. This leads to nigrostriatal degeneration, the main pathogenic mechanism of motor features of Parkinson's disease.SIRT1, a deacetylase enzyme, has neuroprotective effects for Parkinson's disease via targeting various factors. Resveratrol activated SIRT1 can target H3K9 and regulate p53 gene expression at the transcriptional level, thus inhibiting p53 transcription to enhance neuroprtoection, alleviating rotenone induced dopaminergic neurodegeneration. We think these findings should provide a new strategy for the treatment of Parkinson's disease.