A SIRT3/AMPK/autophagy network orchestrates the protective effects of trans-resveratrol in stressed peritoneal macrophages and RAW 264.7 macrophages
A SIRT3/AMPK/autophagy network orchestrates the protective effects of trans-resveratrol in stressed peritoneal macrophages and RAW 264.7 macrophages
复制标题
SIRT3/AMPK/自噬网络协调反式白藜芦醇对应激腹膜巨噬细胞和 RAW 264.7 巨噬细胞的保护作用
DOI：
10.1016/j.freeradbiomed.2016.03.022
复制
发表时间：
2016-06-01
影响因子：
7.4
通讯作者：
He, Rong-Rong
中科院分区：
文献类型：
--
作者：
Duan, Wen-Jun;Li, Yi-Fang;He, Rong-Rong
白藜芦醇因其强大的抗氧化特性而引起人们极大的兴趣，而其对心理社会压力有益作用的分子机制仍然存在争议。在这项研究中，我们证明，白藜芦醇保护腹腔巨噬细胞和RAW 264.7细胞的总细胞计数，吞噬能力，活性氧的产生，单丹酰尸胺和线粒体膜电位在应激小鼠应激诱导的减少。白藜芦醇促进应激诱导的自噬在两种模型中。雷帕霉素或3-甲基腺嘌呤对自噬的调节调节了白藜芦醇的保护作用，表明自噬在白藜芦醇的保护机制中起作用。比较研究表明，白藜芦醇和其他抗氧化剂（维生素C和依达拉奉）的保护作用涉及不同的机制。白藜芦醇通过上调SIRT 3表达和AMP活化蛋白激酶（AMPK）磷酸化来促进自噬。SIRT 3的敲低导致自噬减少，并取消白藜芦醇的保护作用。SIRT 1也参与了白藜芦醇的保护机制，尽管它对自噬的影响并不明显。自噬的药理学操作调节了白藜芦醇对SIRT 3和AMPK的影响，揭示了正反馈回路的参与。与此形成鲜明对比的是，维生素C和依达拉奉有效地保护巨噬细胞免受应激诱导的细胞毒性，同时下调SIRT 3表达和AMPK磷酸化，并降低自噬反应水平。综上所述，我们得出结论，SIRT 3/AMPK/自噬网络协调白藜芦醇在巨噬细胞中的保护作用。(C)2016 Elsevier Inc. All rights reserved.
Resveratrol gains a great interest for its strong antioxidant properties, while the molecular mechanisms underlie the beneficial effects on psychosocial stress remain controversial. In this study, we demonstrated that resveratrol protected peritoneal macrophages and RAW 264.7 cells from stress-induced decrease in the total cell count, phagocytic capability, reactive oxygen species generation, monodansylcadaverine and mitochondrial membrane potential in stressed mice. Resveratrol promoted stress induced autophagy in both models. Modulation of autophagy by rapamycin or 3-methyladenine regulated the protective effect of resveratrol, suggesting a role of autophagy in the protective mechanisms of resveratrol. The comparison studies revealed that distinct mechanisms were implicated in the protective effect of resveratrol and other antioxidants (vitamin C and edaravone). Resveratrol promoted autophagy via upregulating SIRT3 expression and phosphorylation of AMP-activated protein kinase (AMPK). Knockdown of SIRT3 resulted in decreased autophagy and abolished protective effect of resveratrol. SIRT1 was also involved in the protective mechanism of resveratrol, although its effect on autophagy was unnoticeable. Pharmacological manipulation of autophagy modulated the effects of resveratrol on SIRT3 and AMPK, revealing the engagement of a positive feedback loop. In sharp contrast, vitamin C and edaravone effectively protected macrophages from stress-induced cytotoxicity, accompanied by down regulated SIRT3 expression and AMPK phosphorylation, and decreased level of autophagy response. Taken together, we conclude that a SIRT3/AMPK/autophagy network orchestrates in the protective effect of resveratrol in macrophages. (C) 2016 Elsevier Inc. All rights reserved.