Calcium-Sensing Receptor Induced Myocardial Ischemia/Reperfusion Injury via the C-Jun NH2-Terminal Protein Kinase Pathway

Objective: Calcium-sensing receptor (CaSR) belongs to the family C of G-protein coupled receptors. This study was carried out to investigate the role of CaSR in a model of myocardial ischemia/reperfusion injury (MI/RI) in rats. Methods: To produce an MI/RI in rats, a branch of the left anterior descending coronary artery was occluded for 30 min followed by a 6 h reperfusion. Then, we measured cardiac function, noted morphologic alterations of the myocardium, and analyzed the the expression of caspase-3, Bcl-2, CaSR, and c-Jun NH2-terminal protein kinase (JNK) by Western blotting, respectively. Results: GdCl3, an activator of CaSR, further enhanced myocardial injury induced by ischemia/reperfusion, resulting in an increase in JNK phosphorylation, down-regulation of Bcl-2 expression, and up-regulation of caspase-3 expression. Inhibition of JNK activation with SP600125 partly converted the myocardial injury. Conclusion: The results demonstrated that CaSR may induce MI/RI via the INK pathway.