| Post-conditioning protects cardiomyocytes from apoptosis via PKC(epsilon)-interacting with calcium-sensing receptors to inhibit endo(sarco)plasmic reticulum-mitochondria crosstalk. | |
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MedLine Citation:
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PMID: 20383739 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Shiyun Dong; Zongyan Teng; Fang-Hao Lu; Ya-Jun Zhao; Hulun Li; Huan Ren; He Chen; Zhen-Wei Pan; Yan-Jie Lv; Bao-Feng Yang; Ye Tian; Chang-Qing Xu; Wei-Hua Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-11 |
Journal Detail:
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Title: Molecular and cellular biochemistry Volume: 341 ISSN: 1573-4919 ISO Abbreviation: Mol. Cell. Biochem. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-26 Completed Date: 2010-12-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0364456 Medline TA: Mol Cell Biochem Country: Netherlands |
Other Details:
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Languages: eng Pagination: 195-206 Citation Subset: IM |
Affiliation:
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Department of Pathophysiology, Harbin Medical University, Harbin 150086, China. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Apoptosis* Endoplasmic Reticulum / metabolism* Ischemic Postconditioning* Myocytes, Cardiac / cytology* Protein Kinase C-epsilon / metabolism* Rats Rats, Wistar Receptor Cross-Talk Receptors, Calcium-Sensing / metabolism* Signal Transduction |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Calcium-Sensing; EC 2.7.11.13/Protein Kinase C-epsilon |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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