Resveratrol Protects Human Endothelium from H2O2-Induced Oxidative Stress and Senescence via SirT1 Activation
Resveratrol Protects Human Endothelium from H2O2-Induced Oxidative Stress and Senescence via SirT1 Activation
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DOI：
10.5551/jat.4333
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发表时间：
2010-01-01
影响因子：
4.4
通讯作者：
Hwang, Shin-Jang
中科院分区：
文献类型：
--
作者：
Kao, Chung-Lan;Chen, Liang-Kung;Hwang, Shin-Jang
目的：沉默信息调节因子（SirT 1）是一种NAD依赖性组蛋白去乙酰化酶，是正常细胞通过热量限制而延长寿命的重要介质。SirT 1具有多种生物学功能，包括转录调控、细胞分化抑制、细胞周期调控和抗凋亡。白藜芦醇（RV）诱导的SirT 1激活也改善内皮功能障碍，抑制血管炎症。在这项研究中，我们探讨了RV诱导的SirT 1激活内皮细胞氧化stress.Methods的作用：SirT 1 mRNA表达水平进行了检查，从接受冠状动脉旁路移植术（CABG）手术的患者和老年大鼠的心脏冠状动脉血管内皮层（内皮细胞），采用逆转录聚合酶链反应（RT-PCR）。为了进一步探讨SirT 1激活对氧化应激诱导的衰老的影响，衰老相关的β-半乳糖苷酶（SA-β-gal）的表达在RV处理的人脐静脉内皮细胞（HUVECs）与或没有H2 O2处理进行了评估。此外，SirT 1水平在RV处理的HUVEC中呈剂量依赖性增加。SA-β gal检测显示RV抑制H2 O2处理的HUVECs的衰老表型。在siRNA-SirT 1（敲低SirT 1表达）处理的HUVEC细胞中，活性氧（ROS）的产生和SA-β gal阳性细胞的百分比显著增加。结论：SirT 1可能是参与动脉粥样硬化性CAGB患者和衰老大鼠内皮细胞氧化损伤的重要因子。RV是预防氧化应激诱导的内皮细胞衰老的潜在候选药物。RV还可以通过增加内皮SirT 1表达来预防ROS诱导的损伤。
Aim: Silencing information regulator (SirT1), a NAD-dependent histone deacetylase, is an essential mediator of longevity in normal cells by calorie restriction. SirT1 has many biological functions, including transcription regulation, cell differentiation inhibition, cell cycle regulation, and anti-apoptosis. Resveratrol (RV)induced SirT1 activation also improves endothelial dysfunction and suppresses vascular inflammation. In this study, we investigated the roles of RV-induced SirT1 activation in endothelial cells under oxidative stress.Methods: SirT1 mRNA expression levels were examined in the endothelium layer (endothelial cells) of cardiac coronary vessels from patients receiving coronary artery bypass graft surgery (CABG) surgery and aged rats using reverse transcriptase polymerase chain reaction (RT-PCR). To further explore the effect of SirT1 activation on oxidative stress-induced aging, senescence-associated beta-galactosidase (SA-beta-gal) expression in RV-treated human umbilical vein endothelial cells (HUVECs) with or without H2O2 treatment was evaluated.Results: SirT1 expression was decreased in aged and atherosclerotic vessels in vivo, and significantly reduced in endothelial cells purified from vessel tissues. Furthermore, SirT1 levels were dose-dependently increased in RV-treated HUVECs. The SA-beta gal assay showed that RV inhibited the senescent phenotype of H2O2-treated HUVECs. Reactive oxygen species (ROS) production and the percentage of cells positive for SA-beta gal were significantly increased in siRNA-SirT1 (knockdown of SirT1 expression)-treated HUVEC cells. Importantly, the treatment effect of RV was significantly abolished in the oxidative effects of H2O2-treated HUVECs by siRNA-SirT1.Conclusion: Our data suggested that SirT1 could be a crucial factor involved in the endothelial cells of atherosclerotic CAGB patients and aging rats. RV is a potential candidate for preventing oxidative stress-induced aging in endothelial cells. RV may also prevent ROS-induced damage via increased endothelial SirT1 expression.