Induction of SENP1 in myocardium contributes to abnormities of mitochondria and cardiomyopathy

被引：31

作者：

Cai, Rong ^{[1
]}

Gu, Jianmin ^{[2
]}

Sun, Haipeng ^{[3
]}

Liu, Xiaobing ^{[4
]}

Mei, Wenhan ^{[1
]}

Qi, Yitao ^{[5
,6
]}

Xue, Song ^{[2
]}

Ren, Shuxun ^{[7
]}

Rabinowitz, Joseph E. ^{[8
,9
]}

Wang, Yibin ^{[7
]}

Yeh, Edward T. H. ^{[5
,6
]}

Cheng, Jinke ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Tumor Microenvironm & Inflammat, Dept Biochem & Mol Cell Biol, Shanghai 200030, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Renji Hosp, Shanghai 200030, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Minist Educ, Dept Pathophysiol,Key Lab Cell Differentiat & Apo, Shanghai 200030, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Shanghai 200030, Peoples R China

[5] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Cardiol, Houston, TX 77030 USA

[7] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol, Div Mol Med, Los Angeles, CA 90095 USA

[8] Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19122 USA

[9] Temple Univ, Sch Med, Ctr Translat Med, Philadelphia, PA 19122 USA

来源：

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY | 2015年 / 79卷

基金：

中国国家自然科学基金; 上海市自然科学基金;

关键词：

Sentrin/SUMO specific protease 1 (SENP1); Calcium/calcineurin-NFAT3; MEF-2C; PGC-1; alpha; Mitochondria; Cardiac hypertrophy; SUMO-SPECIFIC PROTEASE-1; ENERGY-METABOLISM; HEART-FAILURE; SUMOYLATION; BIOGENESIS; CALCINEURIN; PGC-1-ALPHA; EXPRESSION; COACTIVATORS; MECHANISMS;

D O I：

10.1016/j.yjmcc.2014.11.014

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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.

引用

页码：115 / 122

页数：8

共 45 条

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