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Role of PERK/eIF2 alpha/CHOP Endoplasmic Reticulum Stress Pathway in Oxidized Low-density Lipoprotein Mediated Induction of Endothelial Apoptosis

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单位: [1]Departments of Emergency, China-Japan Friendship Hospital, Beijing 100029, China [2]Beijing Institution ofGeriatrics, Beijing Hospital, Beijing 100730, China [3]Department of Geriatric Medicine, Xiangya Hospital,Central South University, Changsha 410008, Hunan, China [4]Department of Cardiology, TheSecond Xiangya Hospital, Central South University, Changsha 410011, Hunan, China
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关键词: PERK eIF2 alpha CHOP Endoplasmic reticulum stress Oxidized low-density lipoprotein Endothelial cell Apoptosis Atherosclerosis Caspase-3

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Objective PERK/eIF2 alpha/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/eIF2 alpha/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-eIF2 alpha protein expression of primary human umbilical vein endothelial cells (HUVECs) were investigated by Western blot analysis. PERK gene silencing and selective eIF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of eIF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective eIF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/eIF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis. Key words: PERK; eIF2 alpha; CHOP; Endoplasmic reticulum stress; Oxidized low-density lipoprotein; Endothelial cell; Apoptosis; Atherosclerosis; Caspase-3

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出版当年[2015]版:
大类 | 4 区 环境科学与生态学
小类 | 4 区 环境科学 4 区 公共卫生、环境卫生与职业卫生
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 环境科学 4 区 公共卫生、环境卫生与职业卫生
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出版当年[2014]版:
Q2 ENVIRONMENTAL SCIENCES Q2 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH
最新[2023]版:
Q2 ENVIRONMENTAL SCIENCES Q2 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH

影响因子: 最新[2023版] 最新五年平均[2021-2025] 出版当年[2014版] 出版当年五年平均[2010-2014] 出版前一年[2013版] 出版后一年[2015版]

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第一作者单位: [1]Departments of Emergency, China-Japan Friendship Hospital, Beijing 100029, China
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