RGD Reference Report - Post-conditioning protects cardiomyocytes from apoptosis via PKC(epsilon)-interacting with calcium-sensing receptors to inhibit endo(sarco)plasmic reticulum-mitochondria crosstalk. - Rat Genome Database

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Post-conditioning protects cardiomyocytes from apoptosis via PKC(epsilon)-interacting with calcium-sensing receptors to inhibit endo(sarco)plasmic reticulum-mitochondria crosstalk.

Authors: Dong, S  Teng, Z  Lu, FH  Zhao, YJ  Li, H  Ren, H  Chen, H  Pan, ZW  Lv, YJ  Yang, BF  Tian, Y  Xu, CQ  Zhang, WH 
Citation: Dong S, etal., Mol Cell Biochem. 2010 Aug;341(1-2):195-206. doi: 10.1007/s11010-010-0450-5. Epub 2010 Apr 11.
RGD ID: 7206836
Pubmed: PMID:20383739   (View Abstract at PubMed)
DOI: DOI:10.1007/s11010-010-0450-5   (Journal Full-text)

The intracellular Ca(2+) concentration ([Ca(2+)](i)) is increased during cardiac ischemia/reperfusion injury (IRI), leading to endo(sarco)plasmic reticulum (ER) stress. Persistent ER stress, such as with the accumulation of [Ca(2+)](i), results in apoptosis. Ischemic post-conditioning (PC) can protect cardiomyocytes from IRI by reducing the [Ca(2+)](i) via protein kinase C (PKC). The calcium-sensing receptor (CaR), a G protein-coupled receptor, causes the production of inositol phosphate (IP(3)) to increase the release of intracellular Ca(2+) from the ER. This process can be negatively regulated by PKC through the phosphorylation of Thr-888 of the CaR. This study tested the hypothesis that PC prevents cardiomyocyte apoptosis by reducing the [Ca(2+)](i) through an interaction of PKC with CaR to alleviate [Ca(2+)](ER) depletion and [Ca(2+)](m) elevation by the ER-mitochondrial associated membrane (MAM). Cardiomyocytes were post-conditioned after 3 h of ischemia by three cycles of 5 min of reperfusion and 5 min of re-ischemia before 6 h of reperfusion. During PC, PKC(epsilon) translocated to the cell membrane and interacted with CaR. While PC led to a significant decrease in [Ca(2+)](i), the [Ca(2+)](ER) was not reduced and [Ca(2+)](m) was not increased in the PC and GdCl(3)-PC groups. Furthermore, there was no evident psi(m) collapse during PC compared with ischemia/reperfusion (I/R) or PKC inhibitor groups, as evaluated by laser confocal scanning microscopy. The apoptotic rates detected by TUNEL and Hoechst33342 were lower in PC and GdCl(3)-PC groups than those in I/R and PKC inhibitor groups. Apoptotic proteins, including m-calpain, BAP31, and caspase-12, were significantly increased in the I/R and PKC inhibitor groups. These results suggested that PKC(epsilon) interacting with CaR protected post-conditioned cardiomyocytes from programmed cell death by inhibiting disruption of the mitochondria by the ER as well as preventing calcium-induced signaling of the apoptotic pathway.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein kinase binding  IPIPrkce (Rattus norvegicus)7206836 RGD 
signaling receptor binding  IPICasr (Rattus norvegicus)7206836 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Casr  (calcium-sensing receptor)
Prkce  (protein kinase C, epsilon)


Additional Information