Resveratrol Protects against TNF-α-Induced Injury in Human Umbilical Endothelial Cells through Promoting Sirtuin-1-Induced Repression of NF-KB and p38 MAPK.
Resveratrol Protects against TNF-α-Induced Injury in Human Umbilical Endothelial Cells through Promoting Sirtuin-1-Induced Repression of NF-KB and p38 MAPK.
复制标题
白藜芦醇通过促进 Sirtuin-1 诱导的 NF-KB 和 p38 MAPK 抑制来防止 TNF-α 诱导的人脐带内皮细胞损伤
DOI：
10.1371/journal.pone.0147034
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Zhu P
中科院分区：
文献类型：
--
作者：
Pan W;Yu H;Huang S;Zhu P
炎症和活性氧在动脉粥样硬化的发病机制中起重要作用。白藜芦醇具有抗炎和抗氧化应激的作用，但其机制尚不完全清楚。在本研究中，我们研究了白藜芦醇对肿瘤坏死因子-α（TNF-α）诱导的人脐静脉内皮细胞（HUVECs）损伤的保护作用的分子基础，使用多种方法，包括细胞活力测定，逆转录和定量聚合酶链反应，蛋白质印迹和免疫荧光染色。我们发现TNF-α诱导培养的HUVECs中CD 40表达和ROS产生，而白藜芦醇处理可减弱这一作用。此外，白藜芦醇增加sirtuin 1（SIRT 1）的表达;通过小干扰RNA（siRNA）和SIRT 1抑制剂Ex 527抑制SIRT 1降低白藜芦醇对CD 40表达和ROS产生的抑制作用。此外，白藜芦醇下调p65和磷酸化p38 MAPK的水平，但这种抑制作用被SIRT 1活性的抑制减弱。此外，p38 MAPK抑制剂SD 203580和核因子（NF）-κB抑制剂吡咯烷二硫代氨基甲酸酯（PDTC）对TNF-α诱导的ROS生成和CD 40表达的抑制作用与白藜芦醇相似。因此，我们的研究提供了白藜芦醇和SIRT 1激活之间的机制联系，后者参与白藜芦醇介导的p38 MAPK/NF-κB通路的抑制和TNF-α处理的HUVEC中ROS的产生。
Inflammation and reactive oxygen species (ROS) play important roles in the pathogenesis of atherosclerosis. Resveratrol has been shown to possess anti-inflammatory and antioxidative stress activities, but the underlying mechanisms are not fully understood. In the present study, we investigated the molecular basis associated with the protective effects of resveratrol on tumor necrosis factor-alpha (TNF-α)-induced injury in human umbilical endothelial cells (HUVECs) using a variety of approaches including a cell viability assay, reverse transcription and quantitative polymerase chain reaction, western blot, and immunofluorescence staining. We showed that TNF-α induced CD40 expression and ROS production in cultured HUVECs, which were attenuated by resveratrol treatment. Also, resveratrol increased the expression of sirtuin 1 (SIRT1); and repression of SIRT1 by small-interfering RNA (siRNA) and the SIRT1 inhibitor Ex527 reduced the inhibitory effects of resveratrol on CD40 expression and ROS generation. In addition, resveratrol downregulated the levels of p65 and phospho-p38 MAPK, but this inhibitory effect was attenuated by the suppression of SIRT1 activity. Moreover, the p38 MAPK inhibitor SD203580 and the nuclear factor (NF)-κB inhibitor pyrrolidine dithiocarbamate (PDTC) achieved similar repressive effects as resveratrol on TNF-α-induced ROS generation and CD40 expression. Thus, our study provides a mechanistic link between resveratrol and the activation of SIRT1, the latter of which is involved in resveratrol-mediated repression of the p38 MAPK/NF-κB pathway and ROS production in TNF-α-treated HUVECs.