SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection in angiotensin II-induced heart hypertrophy.

SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection in angiotensin II-induced heart hypertrophy.
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SIRT1 在血管紧张素 II 诱导的心脏肥大中充当雌激素介导的心肌细胞保护的重要调节剂。

DOI:
10.1155/2014/713894
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发表时间:
2014
影响因子:
--
通讯作者:
Li J
Li J
中科院分区:
生物学2区
文献类型:
--
作者:
Shen T;Ding L;Ruan Y;Qin W;Lin Y;Xi C;Lu Y;Dou L;Zhu Y;Cao Y;Man Y;Bian Y;Wang S;Xiao C;Li J

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背景Sirtuin 1(SIRT 1)是sirtuin家族的成员,其可以激活细胞存活机制,并且已被证明在调节心脏功能中具有保护作用。在这里,我们确定了SIRT 1调节血管紧张素II-(AngII-)诱导的心肌肥大和损伤在体内和体外的机制。方法.我们分析了SIRT 1在对照组和AngII诱导的肥大小鼠心脏中的表达。切除雌性C57 BL/6小鼠卵巢并用17β-雌二醇预处理以测量SIRT 1表达。对AngII诱导的小鼠心脏肥大样品和培养的新生大鼠心室肌细胞(NRVM)进行蛋白质合成、心肌细胞表面积分析、qRT-PCR、TUNEL染色和Western印迹,以研究SIRT 1的功能。结果SIRT 1表达在AngII诱导的小鼠心脏肥大中轻微上调,伴随着心肌细胞凋亡的增加。SIRT 1过表达减轻AngII诱导的心肌细胞肥大和凋亡17β-雌二醇通过显著上调SIRT 1和激活AMPK来保护心肌细胞免受AngII诱导的损伤。雌激素受体抑制剂ICI 182,780和SIRT 1抑制剂烟酰胺可阻断SIRT 1的保护作用。结论.这些结果表明,SIRT 1功能作为一个重要的调节剂,雌激素介导的心肌细胞保护在血管紧张素II诱导的心脏肥大和损伤。
Background. Sirtuin 1 (SIRT1) is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII-) induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs) to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1's protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury.
DOI: 10.1016/j.tibs.2010.07.003
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