Nmnat2 protects cardiomyocytes from hypertrophy via activation of SIRT6
Nmnat2 protects cardiomyocytes from hypertrophy via activation of SIRT6
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Nmnat2 通过激活 SIRT6 保护心肌细胞免于肥大
DOI：
10.1016/j.febslet.2012.02.014
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发表时间：
2012-03-23
期刊：
影响因子：
3.5
通讯作者：
Liu, Pei-Qing
中科院分区：
文献类型：
--
作者：
Cai, Yi;Yu, Shan-Shan;Liu, Pei-Qing
sirtuins（SIRT）是一个依赖于烟酰胺腺嘌呤二核苷酸（NAD）的去乙酰化酶家族，它的发现表明细胞内NAD水平对心肌细胞的肥大反应至关重要。烟酰胺单核苷酸腺苷酰转移酶（Nmnat）是NAD生物合成的中心酶。在这里，我们发现，Nmnat 2蛋白表达和酶活性在心肌肥厚过程中下调。在新生大鼠心肌细胞中，Nmnat 2的过表达而不是其催化失活突变体阻断了血管紧张素II（Ang II）诱导的心脏肥大，这依赖于通过维持细胞内NAD水平激活SIRT 6。我们的研究结果表明，Nmnat 2活性的调节可能是有益的心肌肥厚。(C)2012年欧洲生物化学学会联合会。Elsevier B.V.出版，保留所有权利。
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.