Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21(WAF1/CIP1), and suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G2.
Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21(WAF1/CIP1), and suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G2.
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发表时间：
1999-06
期刊：
影响因子：
11.2
通讯作者：
T. Hsieh;G. Juan;Z. Darżynkiewicz;Joseph M. Wu
中科院分区：
文献类型：
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作者：
T. Hsieh;G. Juan;Z. Darżynkiewicz;Joseph M. Wu
流行病学研究表明，经常饮用红酒可能部分解释了高脂肪饮食与冠状动脉粥样硬化发病率低的明显相容性。这种现象通常被称为法国悖论，可能与红酒成分有关，红酒成分具有预防肿瘤的特性，并能抑制增加冠心病风险的反应。在这里，我们发现白藜芦醇（红酒中的一种多酚）在培养的肺动脉内皮细胞中诱导一氧化氮合酶（负责 NO 生物合成的酶），表明白藜芦醇可以通过影响一氧化氮合酶的表达来提供心脏保护作用。我们还表明，白藜芦醇抑制肺动脉内皮细胞的增殖，根据流式细胞术分析，这与抑制细胞周期 S 期和 G2 期的细胞进展相关。 Western blot分析和免疫细胞化学蛋白检测结合多参数流式细胞仪进一步证明，S期和G2期的扰动进展伴随着抑癌基因蛋白p53表达的增加和细胞周期蛋白依赖性激酶抑制剂p21（WAF1/CIP1）水平的升高。白藜芦醇所有观察到的作用，包括在较高浓度下诱导细胞凋亡，也与其假定的化学预防和/或抗肿瘤活性相一致。
Epidemiological studies have shown that the regular consumption of red wine may in part account for the apparent compatibility of a high fat diet with a low incidence of coronary atherosclerosis. This phenomenon, commonly referred to as the French paradox, may be associated with red wine constituents that exhibit tumor-preventive properties as well as inhibit reactions that increase the risk of coronary heart disease. Here we show that resveratrol, a polyphenol in red wine, induces nitric oxide synthase, the enzyme responsible for the biosynthesis of NO, in cultured pulmonary artery endothelial cells, suggesting that resveratrol could afford cardioprotection by affecting the expression of nitric oxide synthase. We also show that resveratrol inhibits the proliferation of pulmonary artery endothelial cells, which, based on flow cytometric analysis, correlates with the suppression of cell progression through S and G2 phases of the cell cycle. Western blot analysis and immunocytochemical protein detection combined with multiparameter flow cytometry further demonstrate that the perturbed progression through S and G2 phases is accompanied by an increase in the expression of tumor suppressor gene protein p53 and elevation of the level of cyclin-dependent kinase inhibitor p21(WAF1/CIP1). All of the observed effects of resveratrol, including induction of apoptosis at its higher concentration, are also compatible with its putative chemopreventive and/or antitumor activity.