Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells
Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells
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DOI：
10.1152/ajpheart.00375.2009
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发表时间：
2009-11-01
影响因子：
4.8
通讯作者：
Csiszar, Anna
中科院分区：
文献类型：
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作者：
Ungvari, Zoltan;Labinskyy, Nazar;Csiszar, Anna
Ungvari Z，Labinskyy N，Mukhopadhyay P，平托JT，Bagi Z，Ballabh P，Zhang C，Pacher P，Csiszar A.白藜芦醇减轻冠状动脉内皮细胞线粒体氧化应激。Am J Physiol Heart Circ Physiol 297：H1876-H1881，2009。首次发表于2009年9月11日; doi：10.1152/ajpheart.00375.2009。高血糖诱导的线粒体活性氧（mtROS）的产生是糖尿病并发症发生的关键事件。由于白藜芦醇，一种天然存在的多酚，已被报道赋予血管保护，改善内皮功能和预防糖尿病并发症，我们研究了白藜芦醇对培养的人冠状动脉内皮细胞（CAECs）中线粒体ROS产生的影响。MitoSox荧光的测量结果表明，白藜芦醇减弱稳态和高葡萄糖（30 mM）诱导的线粒体活性氧在CAEC的生产，这是防止蛋白脱乙酰基酶沉默信息调节因子2/沉默调节蛋白1（SIRT 1），白藜芦醇的细胞内目标敲低的效果。SIRT 1的过表达模拟了白藜芦醇的作用，减弱了mtROS的产生。在用靶向H2 O2的H2 O2敏感的Hyper-Mito荧光传感器转染的CAEC中获得了类似的结果。Amplex red检测显示，白藜芦醇和SIRT 1过表达也显着降低了细胞H2 O2水平。白藜芦醇上调MnSOD的表达，并以浓度依赖性的方式增加细胞GSH含量（通过HPLC库仑分析测量）。这些作用被SIRT 1敲低减弱，并被SIRT 1过表达模拟。我们认为，白藜芦醇，通过一个途径，涉及SIRT 1的激活和上调抗氧化防御机制，减弱mtROS的生产，这表明在代谢性疾病中靶向内皮线粒体的新的治疗方法的潜力。
Ungvari Z, Labinskyy N, Mukhopadhyay P, Pinto JT, Bagi Z, Ballabh P, Zhang C, Pacher P, Csiszar A. Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. Am J Physiol Heart Circ Physiol 297: H1876-H1881, 2009. First published September 11, 2009; doi:10.1152/ajpheart.00375.2009. The production of hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) is a key event in the development of diabetic complications. Because resveratrol, a naturally occurring polyphenol, has been reported to confer vasoprotection, improving endothelial function and preventing complications of diabetes, we investigated the effect of resveratrol on mtROS production in cultured human coronary arterial endothelial cells (CAECs). The measurement of MitoSox fluorescence showed that resveratrol attenuates both steady-state and high glucose (30 mM)-induced mtROS production in CAECs, an effect that was prevented by the knockdown of the protein deacetylase silent information regulator 2/sirtuin 1 (SIRT1), an intracellular target of resveratrol. An overexpression of SIRT1 mimicked the effects of resveratrol, attenuating mtROS production. Similar results were obtained in CAECs transfected with mitochondria-targeted H2O2-sensitive HyPer-Mito fluorescent sensor. Amplex red assay showed that resveratrol and SIRT1 overexpression significantly reduced cellular H2O2 levels as well. Resveratrol upregulated MnSOD expression and increased cellular GSH content in a concentration-dependent manner (measured by HPLC coulometric analysis). These effects were attenuated by SIRT1 knockdown and mimicked by SIRT1 overexpression. We propose that resveratrol, via a pathway that involves the activation of SIRT1 and the upregulation of antioxidant defense mechanisms, attenuates mtROS production, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases.