Salubrinal protects against tunicamycin and hypoxia induced cardiomyocyte apoptosis via the PERK-eIF2a signaling pathway  

Salubrinal protects against tunicamycin and hypoxia induced cardiomyocyte apoptosis via the PERK-eIF2α signaling pathway

作　　者：Chun-Lei Liu Xin Li Guo-Liang Hu Rui-Jun Li Yun-Yun He Wu Zhong Song Li Kun-Lun He Li-Li Wang 

机构地区：[1]Department of Cardiology,Chinese PLA General Hospital,28 Fuxing Road,Beijing 100853,China [2]Medical School of Nankai University,74 Weijin Road,Tianjin 300074,China [3]Pharmacy Institute of Military Medical Sciences,27 Taiping Road,Beijing 100850,China

出　　处：《Journal of Geriatric Cardiology》2012年第3期258-268,共11页老年心脏病学杂志（英文版）

基　　金：This study was supported by the Ministry Science Foundation of the Chinese People's Liberation Army during the 12th Five-Year Plan Period

摘　　要：Objectives This study examined the protective effect of salubrinal and the mechanism underlying this protection against tunicamycin （TM）- and hypoxia-induced apoptosis in rat cardiomyocytes. Methods Neonatal rat cardiomyocytes were cultured from the ventricles of l-day-old Wistar rats. Cells were exposed to different concentrations of salubrinal （10, 20, and 40 gmol/L） for 30 min followed by TM treatment or hypoxia for 36 h. Apoptosis was measured by a multiparameter HCS （high content screening） apoptosis assay, TUNEL assay and flow cytometry. The phosphorylation of eukaryotic translation initiation factor 2 subunit alpha （eIF2c0 and the expression of cleaved caspase-12 were determined by Western blotting. C/EBP homologous protein （CHOP） was detected by immunocytochemistry. Results HCS, TUNEL assays and flow cytometry showed that salubrinal protected cardiomyocytes against apoptosis induced by TM or hypoxia. Western blotting showed that salubrinal protected cardiomyocytes against apoptosis by inducing eIF2ct phosphorylation and down-regulating the expression of the endoplasmic reticulum stress-mediated apoptotic proteins, CHOP and cleaved caspase-12. Conclusions Our study suggests that salubrinal protects rat cardiomyocytes against TM- or hypoxia-associated apoptosis via a mechanism involving the inhibition of ER stress-mediated apoptosis.

关 键 词：Endoplasmic reticulum stress Rat cardiomyocytes APOPTOSIS Salubrinal Cell protection 

分 类 号：Q343.1[生物学—遗传学] Q46