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Increased expression of calcium-sensing receptors induced by ox-LDL amplifies apoptosis of cardiomyocytes during simulated ischaemia-reperfusion.

Abstract：

: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.

journal_name

Clin Exp Pharmacol Physiol

journal_title

Clinical and experimental pharmacology & physiology

authors

Guo J,Li HZ,Zhang WH,Wang LC,Wang LN,Zhang L,Li GW,Li HX,Yang BF,Wu L,Wang R,Xu CQ

doi

10.1111/j.1440-1681.2010.05345.x

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

e128-35

issue

eissn

0305-1870

issn

1440-1681

pii

CEP5345

journal_volume

pub_type

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Increased expression of calcium-sensing receptors induced by ox-LDL amplifies apoptosis of cardiomyocytes during simulated ischaemia-reperfusion.