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

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

老年心脏病学杂志(英文版)2012,Vol.9Issue(3):258-268,11.
老年心脏病学杂志(英文版)2012,Vol.9Issue(3):258-268,11.

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

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

Chun-Lei Liu 1Xin Li 2Guo-Liang Hu 1Rui-Jun Li 1Yun-Yun He 1Wu Zhong 1Song Li 2Kun-Lun He 3Li-Li Wang3

作者信息

  • 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
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摘要

Abstract

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 1-day-old Wistar rats. Cells were exposed to different concentrations of salubrinal (10, 20, and 40 μmol/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 (eIF2α) 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 eIF2α 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

Key words

Endoplasmic reticulum stress/Rat cardiomyocytes/Apoptosis/Salubrinal/Cell protection

引用本文复制引用

Chun-Lei Liu,Xin Li,Guo-Liang Hu,Rui-Jun Li,Yun-Yun He,Wu Zhong,Song Li,Kun-Lun He,Li-Li Wang..Salubrinal protects against tunicamycin and hypoxia induced cardiomyocyte apoptosis via the PERK-eIF2α signaling pathway[J].老年心脏病学杂志(英文版),2012,9(3):258-268,11.

基金项目

This study was supported by the Ministry Science Foundation of the Chinese People's Liberation Army during the 12th Five-Year Plan Period (No.BWS12J048). (No.BWS12J048)

老年心脏病学杂志(英文版)

OACSCDSCI

1671-5411

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