Post-conditioning protecting rat cardiomyocytes from apoptosis via attenuating calcium-sensing receptor-induced endo(sarco)plasmic reticulum stress

被引：13

作者：

Gan, Runtao

Hu, Guangxia ^{[1
]}

Zhao, Yajun ^{[1
]}

Li, Hulun ^{[2
]}

Jin, Zhanfeng ^{[3
]}

Ren, Huan ^{[4
]}

Dong, Shiyun ^{[1
]}

Zhong, Xin ^{[1
]}

Li, Hongzhu ^{[1
]}

Yang, Baofeng ^{[5
]}

Xu, Changqing ^{[1
,5
]}

Lu, Fanghao ^{[1
]}

Zhang, Weihua ^{[1
,5
]}

机构：

[1] Harbin Med Univ, Dept Pathophysiol, Harbin 150086, Peoples R China

[2] Harbin Med Univ, Dept Neurobiol, Harbin 150086, Peoples R China

[3] Harbin Med Univ, Dept Pathol, Harbin 150086, Peoples R China

[4] Harbin Med Univ, Dept Immunol, Harbin 150086, Peoples R China

[5] Harbin Med Univ, Biopharmaceut Key Lab Heilongjiang Prov, Harbin 150086, Peoples R China

来源：

MOLECULAR AND CELLULAR BIOCHEMISTRY | 2012年 / 361卷 / 1-2期

基金：

中国国家自然科学基金;

关键词：

Calcium-sensing receptor (CaR); Ischemic post-conditioning; Ischemic/reperfusion; Endoplasmic reticulum stress (ER stress); Heart; ENDOPLASMIC-RETICULUM; CELL-DEATH; REPERFUSION; ACTIVATION; ATF6; INVOLVEMENT; KINASE; INJURY; ER; INHIBITION;

D O I：

10.1007/s11010-011-1096-7

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Our previous studies demonstrated that caclium-sensing receptor (CaR) stimulation elicited phospholipase C (PLC)-mediated inositol triphosphate (IP3) formation, leading to an elevation in [Ca2+] (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, GdCl3, 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 GdCl3, respectively. [Ca2+] (i) and [Ca2+](ER) were determined using Fluo-4 AM and Fluo-5N AM, respectively, using laser confocal microscopy. [Ca2+] (i) was significantly increased, whereas [Ca2+](ER) was significantly decreased in the I/R and PC groups with GdCl3. 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 GdCl3. In the I/R and PC groups with GdCl3, the activated fragments of caspase-12, the cleavage products of activating transcription factor 6 (ATF6) and phospho-JNK (c-Jun NH2-terminal kinase) were increased compared to the PC and PC with GdCl3 groups. These results demonstrated that PC could protect the myocardium from I/R injury by inhibiting CaR-induced sarcoplasmic reticulum stress.

引用

页码：123 / 134

页数：12

共 41 条

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