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
基金:
State Key Clinical Specialty Construction Project, China
语种:
外文
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中科院(CAS)分区:
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
JCR分区:
出版当年[2014]版:
Q2ENVIRONMENTAL SCIENCESQ2PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH
最新[2023]版:
Q2ENVIRONMENTAL SCIENCESQ2PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH
第一作者单位:[1]Departments of Emergency, China-Japan Friendship Hospital, Beijing 100029, China
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推荐引用方式(GB/T 7714):
Tao Yong Kang,Yu Pu Lin,Bai Yong Ping,et al.Role of PERK/eIF2 alpha/CHOP Endoplasmic Reticulum Stress Pathway in Oxidized Low-density Lipoprotein Mediated Induction of Endothelial Apoptosis[J].BIOMEDICAL and ENVIRONMENTAL SCIENCES.2016,29(12):868-876.doi:10.3967/bes2016.116.
APA:
Tao Yong Kang,Yu Pu Lin,Bai Yong Ping,Yan Sheng Tao,Zhao Shui Ping&Zhang Guo Qiang.(2016).Role of PERK/eIF2 alpha/CHOP Endoplasmic Reticulum Stress Pathway in Oxidized Low-density Lipoprotein Mediated Induction of Endothelial Apoptosis.BIOMEDICAL and ENVIRONMENTAL SCIENCES,29,(12)
MLA:
Tao Yong Kang,et al."Role of PERK/eIF2 alpha/CHOP Endoplasmic Reticulum Stress Pathway in Oxidized Low-density Lipoprotein Mediated Induction of Endothelial Apoptosis".BIOMEDICAL and ENVIRONMENTAL SCIENCES 29..12(2016):868-876