Salubrinal protects cardiomyocytes against apoptosis in a rat myocardial infarction model via suppressing the dephosphorylation of eukaryotic translation initiation factor 2α.

Abstract

The aim of the present study was to examine the role of eIF2α in cardiomyocyte apoptosis and evaluate the cardioprotective role of salubrinal in a rat myocardial infarction (MI) model. Rat left anterior descending coronary arteries were ligated and the classical proteins involved in the endoplasmic reticulum stress (ERS)-induced apoptotic pathway were analyzed using quantitative polymerase chain reaction and western blot analysis. Salubrinal was administered to the rats and cardiomyocyte apoptosis and infarct size were evaluated by a specific staining method. Compared with the sham surgery group, the rate of cardiomyocyte apoptosis in the MI group was increased with the development of the disease. It was also demonstrated that the mRNA and protein levels of GRP78, caspase-12, CHOP and the protein expression of p-eIF2α were increased in the MI group. Furthermore, the results showed that treatment with salubrinal can decrease cardiomyocyte apoptosis and infarct size by increasing eIF2α phosphorylation and decreasing the expression of caspase-12 and CHOP. The present study suggests that salubrinal protects against ER stress-induced rat cadiomyocyte apoptosis via suppressing the dephosphorylation of eIF2α in the ERS-associated pathway.

• Authors: Rui-Jun Li, Kun-Lun He, Xin Li, Li-Li Wang, Chun-Lei Liu, Yun-Yun He
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 1 Pg. 1043-9 (Jul 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25816071 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Cinnamates
• Ddit3 protein, rat
• Eukaryotic Initiation Factor-2
• GRP78 protein, rat
• Heat-Shock Proteins
• salubrinal
• Transcription Factor CHOP
• Caspase 12
• Thiourea

Topics

• Animals
• Apoptosis (drug effects, genetics)
• Cardiotonic Agents (pharmacology)
• Caspase 12 (genetics, metabolism)
• Cinnamates (pharmacology)
• Disease Models, Animal
• Disease Progression
• Endoplasmic Reticulum Stress (drug effects, genetics)
• Eukaryotic Initiation Factor-2 (antagonists & inhibitors, genetics, metabolism)
• Gene Expression Regulation
• Heat-Shock Proteins (genetics, metabolism)
• Male
• Myocardial Infarction (drug therapy, genetics, metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Phosphorylation
• Rats
• Rats, Wistar
• Severity of Illness Index
• Signal Transduction
• Thiourea (analogs & derivatives, pharmacology)
• Transcription Factor CHOP (genetics, metabolism)