RGD Reference Report - Calcium-sensing receptor activating phosphorylation of PKCdelta translocation on mitochondria to induce cardiomyocyte apoptosis during ischemia/reperfusion. - Rat Genome Database

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Calcium-sensing receptor activating phosphorylation of PKCdelta translocation on mitochondria to induce cardiomyocyte apoptosis during ischemia/reperfusion.

Authors: Zheng, H  Liu, J  Liu, C  Lu, F  Zhao, Y  Jin, Z  Ren, H  Leng, X  Jia, J  Hu, G  Dong, S  Zhong, X  Li, H  Yang, B  Xu, C  Zhang, W 
Citation: Zheng H, etal., Mol Cell Biochem. 2011 Dec;358(1-2):335-43. doi: 10.1007/s11010-011-0984-1. Epub 2011 Jul 16.
RGD ID: 7205698
Pubmed: PMID:21766206   (View Abstract at PubMed)
DOI: DOI:10.1007/s11010-011-0984-1   (Journal Full-text)

The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) that activates intracellular effectors; for example, it causes inositol phosphate (IP) and 1,2 diacylglycerol (DAG) accumulation, stimulating the release of intracellular calcium and the activation of the protein kinase Cs (PKCs). The activation of CaSR by ischemia/reperfusion (I/R) induces cardiomyocyte apoptosis through the mitochondrial apoptotic pathway; however, the underlying mechanisms remain unclear. In this study, rat hearts were subjected to 30 min of ischemia followed by 2 h of reperfusion in the presence of a CaSR activator, GdCl(3). Our results revealed that, under these conditions, the expression of CaSR was increased, the number of apoptotic cardiomyocytes was significantly increased (as shown by terminal deoxy-nucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay) and the cells with a typical apoptotic morphology were observed using transmission electron microscopy. Our data further showed that mitochondria isolated from hearts that had undergone I/R combined with GdCl(3) exhibited a significant increase in the translocation of phosphorylated PKCdelta to the mitochondria, an increase in cytochrome c (cyt c) release from the mitochondria and a marked decrease in mitochondrial potential. The administration of rottlerin, an inhibitor of PKCdelta, significantly reduced reperfusion-induced apoptosis, phospho-PKCdelta translocation to the mitochondria and the release of cyt c from the mitochondria. Thus, the involvement of CaSR in cardiac apoptosis through the mitochondrial pathway during I/R with GdCl(3) is related to phospho-PKCdelta translocation to the mitochondria.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Myocardial Reperfusion Injury  ISOCasr (Rattus norvegicus)7205698; 7205698protein:increased expression:ventricular myocardium (rat)RGD 
Myocardial Reperfusion Injury  IEP 7205698protein:increased expression:ventricular myocardium (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Casr  (calcium-sensing receptor)

Genes (Mus musculus)
Casr  (calcium-sensing receptor)

Genes (Homo sapiens)
CASR  (calcium sensing receptor)


Additional Information