SUV39H1 mediated SIRT1 trans-repression contributes to cardiac ischemia-reperfusion injury
文献类型: 外文期刊
第一作者: Yang, Guang
作者: Yang, Guang;Zhang, Xinjian;Liang, Peng;Dai, Xin;Zeng, Sheng;Xu, Huihui;Fang, Mingming;Li, Yuehua;Xu, Dachun;Xu, Yong;Weng, Xinyu;Huan, Hailin;Xu, Dachun
作者机构:
关键词: Epigenetics;Ischemia-reperfusion injury;SIRT1;SUV39H1;Transcriptional regulation
期刊名称:BASIC RESEARCH IN CARDIOLOGY ( 影响因子:17.165; 五年影响因子:9.084 )
ISSN: 0300-8428
年卷期: 2017 年 112 卷 3 期
页码:
收录情况: SCI
摘要: Ischemic reperfusion (I/R) contributes to deleterious cardiac remodeling and heart failure. The deacetylase SIRT1 has been shown to protect the heart from I/R injury. We examined the mechanism whereby I/R injury represses SIRT1 transcription in the myocardium. There was accumulation of trimethylated histone H3K9 on the proximal SIRT1 promoter in the myocardium in mice following I/R injury and in cultured cardiomyocytes exposed to hypoxia-reoxygenation (H/R). In accordance, the H3K9 trimethyltransferase SUV39H1 bound to the SIRT1 promoter and repressed SIRT1 transcription. SUV39H1 expression was up-regulated in the myocardium in mice following I/R insults and in H/R-treated cardiomyocytes paralleling SIRT1 down-regulation. Silencing SUV39H1 expression or suppression of SUV39H1 activity erased H3K9Me3 from the SIRT1 promoter and normalized SIRT1 levels in cardiomyocytes. Meanwhile, SUV39H1 deficiency or inhibition attenuated I/R-induced infarction and improved heart function in mice likely through influencing ROS levels in a SIRT1-dependent manner. Therefore, our data uncover a novel mechanism for SIRT1 trans-repression during cardiac I/R injury and present SUV39H1 as a druggable target for the development of therapeutic strategies against ischemic heart disease.
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