The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction
SIRT1的降低通过组蛋白H3K9甲基转移酶影响心肌梗死
Myocardial infarction (MI) dampens heart function and poses a great health risk. The class III deacetylase sirtuin 1 (SIRT1) is known to confer cardioprotection.
心肌梗塞会削弱心脏功能并且带来巨大的健康风险。已知的第三类脱乙酰酶SIRT具有心脏保护作用。
SIRT1 expression is downregulated in the heart by a number of stress stimuli that collectively drive the pathogenesis of MI, although the underlying mechanism remains largely obscure.
SIRT1在心脏中的表达被多种应激刺激下调，这些刺激共同驱动心肌梗死的发病机制，尽管其潜在机制尚不清楚
Here we show that in primary rat neonatal ventricular myocytes (NRVMs), ischaemic or oxidative stress leads to a rapid upregulation of SUV39H, the mammalian histone H3K9 methyltransferase, paralleling SIRT1 downregulation.
我们在这里证明了，原代大鼠新生心室肌细胞中，缺血或氧化应激诱导哺乳动物组蛋白H3K9甲基转移酶SUV39H快速上调，同时伴随SIRT1的下调
Compared to wild-type littermates, SUV39H knockout mice are protected from MI. Likewise, suppression of SUV39H activity with chaetocin attenuates cardiac injury following MI.
与同窝出生的野生型小鼠相比，SUV39H敲除小鼠免于心肌梗死。同样的，用毛霉素抑制SUV39H的活性可减轻心肌梗死后的心脏损伤。
Mechanistically, SUV39H cooperates with heterochromatin protein 1 gamma (HP1g) to catalyse H3K9 trimethylation on the SIRT1 promoter and represses SIRT1 transcription.
在机制上，SUV39H与异染色质蛋白1γ协同催化SIRT1启动子上的H3K9三甲基化，并抑制SIRT1转录
SUV39H augments intracellular ROS levels in a SIRT1-dependent manner. Our data identify a previously unrecognized role for SUV39H linking SIRT1 trans-repression to myocardial infarction.
SUV39H以SIRT依赖的方式增加了细胞内的ROS水平，我们的数据确定了SUV39H和SIRT1反式抑制心肌梗死的新的机制。
