Role of PERK/eIF2α/CHOP Endoplasmic Reticulum Stress Pathway in Oxidized Low-density Lipoprotein Mediated Induction of Endothelial Apoptosis

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• 作者：Yong Kang TAO^aAuthor Vitae ; Pu Lin YU^b ; ^* ; Yong Ping BAI^c ; Sheng Tao YAN^a ; Shui Ping ZHAO^d ; ^{zhaosp@medmail.com.cn} ; Guo Qiang ZHANG^a ; ^{zhangchong2003@vip.sina.com}
• 关键词：PERK ; eIF2α ; CHOP ; Endoplasmic reticulum stress ; Oxidized low-density lipoprotein ; Endothelial cell ; Apoptosis ; Atherosclerosis ; Caspase-3
• 刊名：Biomedical and Environmental Sciences
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：29
• 期：12
• 页码：868-876
• 全文大小：935 K
• 卷排序：29

文摘

PERK/eIF2α/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/eIF2α/CHOP signaling pathway in vascular endothelial cells.MethodsThe effects of ox-LDL on PERK and p-eIF2α protein expression of primary human umbilical vein endothelial cells (HUVECs) were investigated by Western blot analysis. PERK gene silencing and selective eIF2α phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level.ResultsOx-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of eIF2α 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 eIF2α phosphatase inhibitor, salubrinal.ConclusionThis study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/eIF2α/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.