Panax quinquefolium saponin attenuates cardiomyocyte apoptosis induced by thapsigargin through inhibition of endoplasmic reticulum stress

作     者：Mi LIU Mei XUE Xiao-Reng WANG Tian-Qi TAO Fei-Fei XU Xiu-Hua LIU Da-Zhuo SHI 

作者机构：Department of Pathophysiology Chinese PLA General Hospital Beijing China Xiyuan Hospital China Academy of Chinese Medical Sciences Beijing China 

出 版 物：《Journal of Geriatric Cardiology》 (老年心脏病学杂志（英文版）)

年 卷 期：2015年第12卷第5期

页      面：540-546页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 08[工学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 

基　　金：Acknowledgements This work was supported by International Science and Technology Cooperation Project (2010DFA31690)  National Natural Science Foundation of China (81030063 and 81170140) and China Postdoctoral Science Foundation (2014M562608). The authors declare no conflict of interests regarding the publication of this paper 

主　　题：Cardiomyocyte apoptosis Endoplasmic reticulum stress Panax quinqueJblium saponin Thapsigargin 

摘      要：Background Endoplasmic reticulum （ER） stress-related apoptosis is involved in the pathophysiology of many cardiovascular diseases, and Panax quinquefolium saponin （PQS） is able to inhibit excessive ER stress-related apoptosis of cardiomyocytes following hypoxia/reoxygenation and myocardial infarction. However, the pathway by which PQS inhibits the ER stress-related apoptosis is not well understood. To further investigate the protective effect of PQS against ER stress-related apoptosis, primary cultured eardiomyocytes were stimulated with thapsigargin （TG）, which is widely used to model cellular ER stress, and it could induce apoptotic cell death in sufficient concentration. Methods Primary cultured cardiomyocytes from neonatal rats were exposed to TG （1 μmol/L） treatment for 24 h, following PQS pre-treatment （160 μg/mL） for 24 h or pre-treatment with small interfering RNA directed against protein kinase-like endoplasmic reticulum kinase （Si-PERK） for 6 h. The viability and apoptosis rate of cardiomyocytes were detected by cell counting kit-8 and flow cytometry respectively. ER stress-related protein expression, such as glucose-regulated protein 78 （GRP78）, calreticulin, PERK, eukaryotic translation initiation factor 2α （elF2c0, activating transcription factor 4 （ATF4）, and C/EBP homologous protein （CHOP） were assayed by western blotting. Results Both PQS pre-treatment and PERK knockdown remarkably inhibited the cardiomyocyte apoptosis induced by TG, increased cell viability, decreased phosphorylation of both PERK and eIF2α, and decreased protein levels of both ATF4 and CHOP. There was no statistically significant difference between PQS pre-treatment and PERK knockdown in the cardioprotective effect. Conclusions Our data indicate that the PERK-eIF2α-ATF4-CHOP pathway of ER stress is involved in the apoptosis induced by TG, and PQS might prevent TG-induced cardiomyocyte apoptosis through a mechanism involving the suppression of this pathway. These findings provide nov