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01.05.2017 | Original Contribution

SUV39H1 mediated SIRT1 trans-repression contributes to cardiac ischemia–reperfusion injury

verfasst von: Guang Yang, Xinjian Zhang, Xinyu Weng, Peng Liang, Xin Dai, Sheng Zeng, Huihui Xu, Hailin Huan, Mingming Fang, Yuehua Li, Dachun Xu, Yong Xu

Erschienen in: Basic Research in Cardiology | Ausgabe 3/2017

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Abstract

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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Titel: SUV39H1 mediated SIRT1 trans-repression contributes to cardiac ischemia–reperfusion injury
verfasst von: Guang Yang
Xinjian Zhang
Xinyu Weng
Peng Liang
Xin Dai
Sheng Zeng
Huihui Xu
Hailin Huan
Mingming Fang
Yuehua Li
Dachun Xu
Yong Xu
Publikationsdatum: 01.05.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Basic Research in Cardiology / Ausgabe 3/2017
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-017-0608-3

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SUV39H1 mediated SIRT1 trans-repression contributes to cardiac ischemia–reperfusion injury

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