ISCHEMIC POSTCONDITIONING PROTECTS MYOCARDIUM FROM ISCHEMIA/REPERFUSION INJURY THROUGH ATTENUATING ENDOPLASMIC RETICULUM STRESS

Abstract

Ischemic postconditioning (I-postC) is a newly discovered endogenous protective phenomenon capable of protecting the myocardium from I/R injury. The cardioprotective mechanisms of I-postC involve protein synthesis and preventing an increase in cytosolic calcium. Endoplasmic reticulum (ER) is a principal site for secretory protein synthesis and calcium storage. Myocardial I/R causes ER stress and perturbations of ER function. The purpose of the present study was to determine whether I-postC's attenuation of I/R injury involves reductions in ER stress through mitogen-activated protein kinase (MAPK) pathway. In the present study, models of rat myocardial I/R and hypoxia/reoxygenation (H/R) of neonatal rat cardiomyocytes were used. Myocardial infarct size was measured by triphenyltetrazolium chloride staining, and flow cytometry was used to quantitate cardiomyocyte apoptosis. Calreticulin expression and activation of caspase 12, p38 MAPK, and c-Jun NH2-terminal kinase (JNK) in myocardium or cardiomyocytes were detected by Western blots. It is found that I-postC protects the I/R heart against myocardial infarction, and hypoxic postconditioning protects neonatal cardiomyocytes from H/R-induced apoptosis. Ischemic postconditioning suppressed I/R-induced ER stress, as shown by a decrease in calreticulin expression and caspase 12 activation. Hypoxic postconditioning up-regulates p38 MAPK phosphorylation and down-regulates JNK phosphorylation in cardiomyocytes subjected to H/R. These results indicate that I-postC protects myocardium from I/R injury by suppressing ER stress, and that p38 MAPK and JNK pathways are associated with the I-postC-induced suppression of ER stress.