Cheng Tzu-Hurng, Liu Ju-Chi, Lin Heng, Shih Neng-Lang, Chen Yen-Ling, Huang Meng-Ting, Chan Paul, Cheng Ching-Feng, Chen Jin-Jer
Department of Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan, Republic of China.
Naunyn Schmiedebergs Arch Pharmacol. 2004 Feb;369(2):239-44. doi: 10.1007/s00210-003-0849-6. Epub 2003 Dec 9.
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 [3H]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.
白藜芦醇被认为是红酒对心血管系统具有保护作用的部分原因。血管紧张素II(Ang II)是心肌细胞中一种强大的肥大刺激因子。在本研究中,我们确定了白藜芦醇对Ang II诱导的心肌细胞肥大的影响。用Ang II刺激培养的新生大鼠心肌细胞,并检测[3H]亮氨酸掺入和β-肌球蛋白重链(β-MyHC)启动子活性。通过氧化还原敏感荧光染料2',7'-二氯荧光素二乙酸酯测量细胞内活性氧(ROS),并通过蛋白质印迹法检测细胞外信号调节激酶(ERK)磷酸化。白藜芦醇抑制Ang II升高的细胞内ROS水平。此外,白藜芦醇以及抗氧化剂N-乙酰半胱氨酸可降低Ang II或H2O2升高的蛋白质合成、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弱ROS生成来抑制Ang II诱导的心肌细胞肥大。