Inhibitory effect of resveratrol on angiotensin II-induced cardiomyocyte hypertrophy

Inhibitory effect of resveratrol on angiotensin II-induced cardiomyocyte hypertrophy
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DOI:
10.1007/s00210-003-0849-6
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发表时间:
2004-02-01
影响因子:
3.6
通讯作者:
Chen, JJ
Chen, JJ
中科院分区:
医学4区
文献类型:
--
作者:
Cheng, TH;Liu, JC;Chen, JJ

文献摘要

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白藜芦醇被认为是红酒对心血管系统保护作用的部分原因。血管紧张素II(AngII)是心肌细胞的一种强有力的肥大刺激物。在这项研究中,我们确定了白藜芦醇对血管紧张素II诱导的心肌细胞肥大的影响。培养的新生大鼠心肌细胞与血管紧张素II刺激,[H-3]亮氨酸掺入和β-肌球蛋白重链(β-MyHC)启动子活性进行了检查。用2'7'-二氯荧光素二乙酸酯(2'7'-dichlorofluorescindiacetate)检测细胞内活性氧(reactiveoxygenspecies,ROS),用Western blotting检测细胞外信号调节激酶(extracellularsignal-regulatedkinase,ERK)磷酸化水平。白藜芦醇抑制血管紧张素II增加细胞内ROS水平。此外,白藜芦醇,以及抗氧化剂N-乙酰半胱氨酸,降低血管紧张素II-或H2 O2-增加蛋白质合成,β-MyHC启动子活性,和ERK磷酸化。总之,我们首次证明白藜芦醇通过减少ROS的产生来抑制血管紧张素II诱导的心肌细胞肥大。
Resveratrol is proposed to account in part for the protective effect of red wine on the cardiovascular system. Angiotensin II (Ang II) is a potent hypertrophic stimulus in cardiomyocytes. In this study, we determined the effect of resveratrol on Ang II-induced cardiomyocyte hypertrophy. Cultured neonatal rat cardiomyocytes were stimulated with Ang II, and [H-3]leucine incorporation and beta-myosin heavy chain (beta-MyHC) promoter activity were examined. Intracellular reactive oxygen species (ROS) were measured by a redox-sensitive fluorescent dye, 2' 7'-dichlorofluorescin diacetate, and the extracellular signal-regulated kinase (ERK) phosphorylation was examined by Western blotting. Resveratrol inhibited Ang II-increased intracellular ROS levels. Furthermore, resveratrol, as well as the antioxidant N-acetyl-cysteine, decreased Ang II- or H2O2-increased protein synthesis, beta-MyHC promoter activity, and ERK phosphorylation. In summary, we demonstrate for the first time that resveratrol inhibits Ang II-induced cardiomyocyte hypertrophy via attenuation of ROS generation.