Yong Kang Tao1, Pu Lin Yu2, Yong Ping Bai3, Sheng Tao Yan1, Shui Ping Zhao4, Guo Qiang Zhang1. 1. Departments of Emergency, China-Japan Friendship Hospital, Beijing 100029, China. 2. Beijing Institution of Geriatrics, Beijing Hospital, Beijing 100730, China. 3. Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China. 4. Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
Abstract
OBJECTIVE: 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. METHODS: The 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. RESULTS: Ox-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. CONCLUSION: This 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.
OBJECTIVE: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. METHODS: The 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. RESULTS: Ox-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. CONCLUSION: This 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.
Authors: F Luchetti; R Crinelli; E Cesarini; B Canonico; L Guidi; C Zerbinati; G Di Sario; L Zamai; M Magnani; S Papa; L Iuliano Journal: Redox Biol Date: 2017-07-29 Impact factor: 11.799
Authors: Yeh Siang Lau; Mohd Rais Mustafa; Ker Woon Choy; Stanley M H Chan; Simon Potocnik; Terence P Herbert; Owen L Woodman Journal: Sci Rep Date: 2018-01-29 Impact factor: 4.379