Post-conditioning Protecting Rat Cardiomyocytes from Apoptosis Via Attenuating Calcium-sensing Receptor-induced Endo(sarco)plasmic Reticulum Stress

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2011 Oct 11

PMID 21984037

Citations 6

Authors

Runtao Gan

Guangxia Hu

Yajun Zhao

Hulun Li

Zhanfeng Jin

Huan Ren

Shiyun Dong

Xin Zhong

Hongzhu Li

Baofeng Yang

Changqing Xu

Fanghao Lu

Weihua Zhang

Affiliations

Soon will be listed here.

Abstract

Our previous studies demonstrated that caclium-sensing receptor (CaR) stimulation elicited phospholipase C (PLC)-mediated inositol triphosphate (IP(3)) formation, leading to an elevation in [Ca(2+)](i) released from the endo(sarco)plasmic reticulum (ER) to induce ER stress and perturbations of ER function, which cause cardiomyocyte apoptosis during ischemia/reperfusion (I/R). The aim of this study was to determine whether the protection of post-conditioning (PC) from I/R heart injury involved relieving calcium-sensing receptor (CaR)-induced ER stress. Male Wistar rats were subjected to 30 min of ischemia followed by 2 h of reperfusion. The rats were post-conditioned after the 30 min of ischemia by three cycles of 10 s of reperfusion followed by 10 s of ischemia at the onset of reperfusion. Meanwhile, GdCl(3), an activator of CaR, and NPS-2390, a specific inhibitor, were administered. We found that the PC and PC with NPS-2390 groups improved the recovery of cardiac function during reperfusion compared to the IR and PC groups with GdCl(3), respectively. [Ca(2+)](i) and [Ca(2+)](ER) were determined using Fluo-4 AM and Fluo-5N AM, respectively, using laser confocal microscopy. [Ca(2+)](i) was significantly increased, whereas [Ca(2+)](ER) was significantly decreased in the I/R and PC groups with GdCl(3). The rate of apoptotic cells was significantly decreased as shown by TUNEL (Terminal deoxy-nucleotidyl transferase-mediated dUTP nick end labeling) assay in PC and PC with NPS-2390 groups compared to the I/R and PC groups with GdCl(3). In the I/R and PC groups with GdCl(3), the activated fragments of caspase-12, the cleavage products of activating transcription factor 6 (ATF6) and phospho-JNK (c-Jun NH(2)-terminal kinase) were increased compared to the PC and PC with GdCl(3) groups. These results demonstrated that PC could protect the myocardium from I/R injury by inhibiting CaR-induced sarcoplasmic reticulum stress.

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