title: Induction of autophagy by salidroside through the AMPK-mTOR pathway protects vascular endothelial cells from oxidative stress-induced apoptosis.
abstract: Vascular endothelial cells are highly sensitive to oxidative stress, and this is one of the mechanisms by which widespread endothelial dysfunction is induced in most cardiovascular diseases and disorders. However, how these cells can survive in oxidative stress environments remains unclear. Salidroside, a traditional Chinese medicine, has been shown to confer vascular protective effects. We aimed to understand the role of autophagy and its regulatory mechanisms by treating human umbilical vein endothelial cells (HUVECs) with salidroside under oxidative stress. HUVECs were treated with salidroside and exposed to hydrogen peroxide (H2O2). The results indicated that salidroside exerted cytoprotective effects in an H2O2-induced HUVEC injury model and suppressed H2O2-induced apoptosis of HUVECs. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, increased oxidative stress-induced HUVEC apoptosis, while the autophagy activator rapamycin induced anti-apoptosis effects in HUVECs. Salidroside increased autophagy and decreased apoptosis of HUVECs in a dose-dependent manner under oxidative stress. Moreover, 3-MA attenuated salidroside-induced HUVEC autophagy and promoted apoptosis, whereas rapamycin had no additional effects compared with salidroside alone. Salidroside upregulated AMPK phosphorylation but downregulated mTOR phosphorylation under oxidative stress; however, administration of compound C, an AMPK inhibitor, abrogated AMPK phosphorylation and increased mTOR phosphorylation and apoptosis compared with salidroside alone. These results suggest that autophagy is a protective mechanism in HUVECs under oxidative stress and that salidroside might promote autophagy through activation of the AMPK pathway and downregulation of mTOR pathway.
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Xiang-Tao
authors.initials: XT
authors.lastname: Zheng
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Zi-Heng
authors.initials: ZH
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Ju-Ji
authors.initials: JJ
authors.lastname: Dai
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
authors.forename: Guan-Feng
authors.initials: GF
authors.lastname: Yu
authors.affiliation: Department of Central Laboratory, The third Hospital Affiliated to Nantong University, Wuxi, 214041, Jiangsu, People's Republic of China. wangyu3h@163.com.
authors.forename: FengLai
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Oncological Surgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou, 325015, Zhejiang, People's Republic of China. yljwenzhou@126.com.
authors.forename: Le-Chi
authors.initials: LC
authors.lastname: Ye
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D005960:Glucosides / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000201:enzymology*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D005960:Glucosides; D010636:Phenols; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C009172:rhodioloside
keywords: Autophagy; Oxidative stress; Salidroside; Signaling pathway; Vascular endothelial cells