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Increased expression of calcium‐sensing receptors induced by ox‐LDL amplifies apoptosis of cardiomyocytes during simulated ischaemia–reperfusion
Author(s) -
Guo Jin,
Li HongZhu,
Zhang WeiHua,
Wang LuChuan,
Wang LiNa,
Zhang Li,
Li GuangWei,
Li HongXia,
Yang BaoFeng,
Wu Lingyun,
Wang Rui,
Xu ChangQing
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2010.05345.x
Subject(s) - calcium sensing receptor , apoptosis , calcium in biology , ischemia , agonist , downregulation and upregulation , medicine , endocrinology , receptor , cytochrome c , intracellular , calcium , antagonist , reperfusion injury , chemistry , calcium metabolism , biology , microbiology and biotechnology , biochemistry , gene
Summary 1. Acute myocardial infarction (AMI) is strongly associated with atherosclerosis, and is responsible for significant morbidity and mortality worldwide. The pathogenic mechanisms that underlie atherosclerosis and AMI are undefined at present. The calcium‐sensing receptor (CaSR) is a member of the superfamily of G‐protein coupled receptors. It has been demonstrated previously that the expression of CaSR is increased in atherosclerotic cardiac tissue of rats. It has also been suggested that CaSR has a crucial role in cardiac ischaemia–reperfusion injury, apoptosis and hypertrophy. However, it remains to be determined whether an increase in the expression of CaSR influences the sensitivity of cardiomyocytes to AMI. 2. The present study used cultured ventricular cardiomyocytes from neonatal rats to investigate the effect of oxidized low‐density lipoprotein (ox‐LDL), ischaemia–reperfusion, GdCl 3 (an agonist of CaSR) and NPS‐2390 (an antagonist of CaSR) on the expression of CaSR. The amount of apoptosis, alterations in the morphology of the cells, the intracellular calcium concentration ([Ca 2+ ] i ) and components of critical mitochondrial pathways were also analysed. 3. Cardiomyocytes treated with ox‐LDL showed upregulated expression of CaSR, cytochrome c (cyt‐c), Bax and activated caspase 3 (17 kD) and downregulated expression of Bcl‐2, as well as elevated [Ca 2+ ] i and apoptosis. Application of GdCl 3 augmented these effects, and NPS‐2390 decreased the expression of CaSR and reduced apoptosis. 4. In conclusion, ox‐LDL was found to increase the expression of CaSR in a manner that was dependent on time and dose. It also augmented apoptosis during simulated ischaemia–reperfusion in cultured ventricular cardiomyocytes from neonatal rats.