Nmnat2 protects cardiomyocytes from hypertrophy via activation of SIRT6

被引：85

作者：

Cai, Yi ^{[1
]}

Yu, Shan-Shan ^{[2
]}

Chen, Shao-Rui ^{[1
]}

Pi, Rong-Biao ^{[1
]}

Gao, Si ^{[1
]}

Li, Hong ^{[1
]}

Ye, Jian-Tao ^{[1
]}

Liu, Pei-Qing ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Dept Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China

[2] So Med Univ, Zhujiang Hosp, Dept Pharmaceut Sci, Guangzhou 510280, Guangdong, Peoples R China

来源：

FEBS LETTERS | 2012年 / 586卷 / 06期

基金：

中国国家自然科学基金;

关键词：

Nmnat2; Cardiac hypertrophy; Sirtuin; 6; NAD; Ang II; UBIQUITIN-PROTEASOME PATHWAY; NONSENSE-MEDIATED DECAY; CARDIAC-HYPERTROPHY; HEART-FAILURE; NAD(+); SIRTUINS; DISEASE; STRESS; TRANSCRIPTION; DYSFUNCTION;

D O I：

10.1016/j.febslet.2012.02.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The discovery of sirtuins (SIRT), a family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, has indicated that intracellular NAD level is crucial for the hypertrophic response of cardiomyocytes. Nicotinamide mononucleotide adenylyltransferase (Nmnat) is a central enzyme in NAD biosynthesis. Here we revealed that Nmnat2 protein expression and enzyme activity were down-regulated during cardiac hypertrophy. In neonatal rat cardiomyocytes, overexpression of Nmnat2 but not its catalytically inactive mutant blocked angiotensin II (Ang II)-induced cardiac hypertrophy, which was dependent on activation of SIRT6 through maintaining the intracellular NAD level. Our results suggested that modulation of Nmnat2 activity may be beneficial in cardiac hypertrophy. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：866 / 874

页数：9

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