Involvement of calcium-sensing receptor in ischemia/reperfusion-induced apoptosis in rat cardiomyocytes

Journal Article · Fri Sep 08 04:00:00 EDT 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.06.176· OSTI ID:20854445

Weihua, Zhang ^[1]; Songbin, Fu ^[2]; Fanghao, Lu ^[1]; Bo, Wu ^[1]; Dongmei, Gong ^[3]; Pan, Zhen-wei ^[3]; Yanjie, Lv ^[3]; Yajun, Zhao ^[1]; Quanfeng, Li ^[1]; Rui, Wang ^[1]; Baofeng, Yang ^[3]; Changqing, Xu ^[4]

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1. Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China)
2. Department of Genetics, Harbin Medical University, Harbin 150086 (China)
3. Department of Pharmacology, Harbin Medical University, Harbin 150086 (China)
4. Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China) and Bio-pharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150086 (China)

The calcium-sensing receptor (CaR) is a seven-transmembrane G-protein coupled receptor, which activates intracellular effectors, for example, it causes inositol phosphate (IP) accumulation to increase the release of intracellular calcium. Although intracellular calcium overload has been implicated in the cardiac ischemia/reperfusion (I/R)-induced apoptosis, the role of CaR in the induction of apoptosis has not been fully understood. This study tested the hypothesis that CaR is involved in I/R cardiomyocyte apoptosis by increasing [Ca{sup 2+}]{sub i}. The isolated rat hearts were subjected to 40-min ischemia followed by 2 h of reperfusion, meanwhile GdCl{sub 3} was added to reperfusion solution. The expression of CaR increased at the exposure to GdCl{sub 3} during I/R. By laser confocal microscopy, it was observed that the intracellular calcium was significantly increased and exhibited a collapsed {delta}{psi} {sub m}, as monitored by 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolcarbocyanine iodide (JC-1) during reperfusion with GdCl{sub 3}. Furthermore, the number of apoptotic cells was significantly increased as shown by TUNEL assay. Typical apoptotic cells were observed with transmission electron microscopy in I/R with GdCl{sub 3} but not in the control group. The expression of cytosolic cytochrome c and activated caspase-9 and caspase-3 was significantly increased whereas the expression of mitochondrial cytochrome c significantly decreased in I/R with GdCl{sub 3} in comparison to the control. In conclusion, these results suggest that CaR is involved in the induction of cardiomyocyte apoptosis during ischemia/reperfusion through activation of cytochrome c-caspase-3 signaling pathway.

• OSTI ID: 20854445
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 347; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CALCIUM
GADOLINIUM CHLORIDES
GTP-ASES
INOSITOL
ISCHEMIA
RATS
RECEPTORS
TRANSMISSION ELECTRON MICROSCOPY