Curcumin induces autophagy to protect vascular endothelial cell survival from oxidative stress damage
Curcumin induces autophagy to protect vascular endothelial cell survival from oxidative stress damage
复制标题
姜黄素诱导自噬以保护血管内皮细胞免受氧化应激损伤
DOI：
10.4161/auto.19471
复制
发表时间：
2012-05-01
期刊：
影响因子：
13.3
通讯作者：
Li, Xue-Jun
中科院分区：
文献类型：
--
作者：
Han, Jing;Pan, Xue-Yang;Li, Xue-Jun
我们的研究首次提出姜黄素可以通过自噬保护人内皮细胞免受氧化应激的损伤。此外，我们的研究结果表明，姜黄素引起一些新的细胞机制，促进自噬作为一种保护作用。姜黄素预处理显着提高人脐静脉内皮细胞（HUVECs）的生存从过氧化氢诱导的活力丧失，这特别引起自噬反应。暴露于H2 O2，姜黄素处理的HUVECs上调微管相关蛋白1轻链3-II（LC 3-II）的水平，自噬体的数量和p62的降解。我们表明，这种化合物促进BECN 1表达，抑制磷脂酰肌醇3-激酶（PtdIns 3 K）-AKT-雷帕霉素（MTOR）信号通路的机制目标。姜黄素还可以逆转FOXO 1（自噬介体）的核定位，沿着引起FOXO 1的胞质乙酰化水平升高以及乙酰化FOXO 1与ATG 7的相互作用。此外，通过shRNA敲低FOXO 1不仅抑制姜黄素诱导的保护作用，而且抑制自噬过程，从LC 3-II的数量到RAB 7的表达。这些结果表明，姜黄素诱导自噬，表明姜黄素有可能用作自噬相关的抗氧化剂，用于预防和治疗氧化应激。这些数据揭示了一种全新的保护机制，涉及FOXO 1在调节HUVEC中的自噬中具有关键作用，并表明姜黄素在诱导HUVEC中有益形式的自噬中具有新的作用，这可能是治疗氧化应激相关心血管疾病的潜在多靶点治疗途径。
Our study first proposed that curcumin could protect human endothelial cells from the damage caused by oxidative stress via autophagy. Furthermore, our results revealed that curcumin causes some novel cellular mechanisms that promote autophagy as a protective effect. Pretreatment with curcumin remarkably improves the survival of human umbilical vein endothelial cells (HUVECs) from H2O2-induced viability loss, which specifically evokes an autophagic response. Exposed to H2O2, curcumin-treated HUVECs upregulate the level of microtubule-associated protein 1 light chain 3-II (LC3-II), the number of autophagosomes, and the degradation of p62. We show that this compound promotes BECN1 expression and inhibits the phosphatidylinositol 3-kinase (PtdIns3K)-AKT-mechanistic target of rapamycin (MTOR) signaling pathway. Curcumin can also reverse FOXO1 (a mediator of autophagy) nuclear localization along with causing an elevated level of cytoplasmic acetylation of FOXO1 and the interaction of acetylated FOXO1 and ATG7, under the circumstance of oxidative stress. Additionally, knockdown of FOXO1 by shRNA inhibits not only the protective effects that curcumin induced, but the autophagic process, from the quantity of LC3-II to the expression of RAB7. These results suggest that curcumin induces autophagy, indicating that curcumin has the potential for use as an autophagic-related antioxidant for prevention and treatment of oxidative stress. These data uncover a brand new protective mechanism involving FOXO1 as having a critical role in regulating autophagy in HUVECs, and suggest a novel role for curcumin in inducing a beneficial form of autophagy in HUVECs, which may be a potential multitargeted therapeutic avenue for the treatment of oxidative stress-related cardiovascular diseases.