Induction of SENP1 in myocardium contributes to abnormities of mitochondria and cardiomyopathy
Induction of SENP1 in myocardium contributes to abnormities of mitochondria and cardiomyopathy
复制标题
心肌中SENP1的诱导导致线粒体异常和心肌病
DOI：
10.1016/j.yjmcc.2014.11.014
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发表时间：
2015-02-01
影响因子：
5
通讯作者：
Cheng, Jinke
中科院分区：
文献类型：
--
作者：
Cai, Rong;Gu, Jianmin;Cheng, Jinke
线粒体生物合成和心脏能量代谢的缺陷是心脏肥大和心力衰竭的关键因素。Sentrin/SUMO特异性蛋白酶1（SENP 1）介导的PGC-1 α转录活性调节在线粒体生物发生和线粒体功能中发挥着重要作用。然而，SENP 1是否在心脏肥大和衰竭中起作用尚不清楚。我们研究了SENP 1表达的改变是否影响心肌病及其潜在机制。在我们目前的研究中，我们发现SENP 1的表达在小鼠和人类衰竭心脏中被诱导，与线粒体基因的诱导表达相关。心肌细胞中的SENP 1表达通过钙/钙调神经磷酸酶-NFAT 3由肥大刺激诱导。SENP 1通过MEF-2C的去SUMO化调节线粒体基因表达，这增强了MEF-2C介导的PGC-1 α转录。SENP 1的遗传诱导导致体内线粒体失调和心脏功能障碍。我们的数据表明，心肌病的发病机制归因于SENP 1介导的线粒体异常的调节。SENP 1在病变心脏中的上调通过钙调神经磷酸酶-NFAT/MEF 2C-PGC-1 α途径介导。(C)2014爱思唯尔有限公司版权所有。
Defect in mitochondrial biogenesis and cardiac energy metabolism is a critical contributing factor to cardiac hypertrophy and heart failure. Sentrin/SUMO specific protease 1 (SENP1) mediated regulation of PGC-1 alpha transcriptional activity plays an essential role in mitochondrial biogenesis and mitochondrial function. However, whether SENP1 plays a role in cardiac hypertrophy and failure is unknown. We investigated whether alteration in SENP1 expression affects cardiomyopathy and the underlying mechanism. In our present study, we found that the expression of SENP1 was induced in mouse and human failing hearts associated with induced expression of mitochondrial genes. SENP1 expression in cardiomyocytes was induced by hypertrophic stimuli through calcium/calcineurin-NFAT3. SENP1 regulated mitochondrial gene expression by de-SUMOylation of MEF-2C, which enhanced MEF-2C-mediated PGC-1 alpha transcription. Genetic induction of SENP1 led to mitochondrial dysregulation and cardiac dysfunction in vivo. Our data showed that pathogenesis of cardiomyopathy is attributed by SENP1 mediated regulation of mitochondrial abnormities. SENP1 up-regulation in diseased heart is mediated via calcineurin-NFAT/MEF2C-PGC-1 alpha pathway. (C) 2014 Elsevier Ltd. All rights reserved.