PMID- 21766206
OWN - NLM
STAT- MEDLINE
DCOM- 20120221
LR  - 20211020
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 358
IP  - 1-2
DP  - 2011 Dec
TI  - Calcium-sensing receptor activating phosphorylation of PKCdelta translocation on 
      mitochondria to induce cardiomyocyte apoptosis during ischemia/reperfusion.
PG  - 335-43
LID - 10.1007/s11010-011-0984-1 [doi]
AB  - 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.
FAU - Zheng, Huishuang
AU  - Zheng H
AD  - Department of Pathophysiology, Harbin Medical University, Harbin 150086, China.
FAU - Liu, Jun
AU  - Liu J
FAU - Liu, Chong
AU  - Liu C
FAU - Lu, Fanghao
AU  - Lu F
FAU - Zhao, Yajun
AU  - Zhao Y
FAU - Jin, Zhanfeng
AU  - Jin Z
FAU - Ren, Huan
AU  - Ren H
FAU - Leng, Xiaoning
AU  - Leng X
FAU - Jia, Jing
AU  - Jia J
FAU - Hu, Guangxia
AU  - Hu G
FAU - Dong, Shiyun
AU  - Dong S
FAU - Zhong, Xin
AU  - Zhong X
FAU - Li, Hongzhu
AU  - Li H
FAU - Yang, Baofeng
AU  - Yang B
FAU - Xu, Changqing
AU  - Xu C
FAU - Zhang, Weihua
AU  - Zhang W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110716
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 0 (extracellular calcium cation-sensing receptor, rat)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 2.7.1.- (Prkcd protein, rat)
RN  - EC 2.7.11.13 (Protein Kinase C-delta)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Blotting, Western
MH  - Calcium/metabolism
MH  - Cytochromes c/metabolism
MH  - In Situ Nick-End Labeling
MH  - Intracellular Space/metabolism
MH  - Male
MH  - Microscopy, Confocal
MH  - Mitochondria, Heart/*enzymology/ultrastructure
MH  - Myocardial Reperfusion Injury/*enzymology/*pathology
MH  - Myocardium/enzymology/ultrastructure
MH  - Myocytes, Cardiac/enzymology/*pathology/ultrastructure
MH  - Phosphorylation
MH  - Protein Kinase C-delta/*metabolism
MH  - Protein Transport
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Calcium-Sensing/*metabolism
MH  - Subcellular Fractions/metabolism
EDAT- 2011/07/19 06:00
MHDA- 2012/02/22 06:00
CRDT- 2011/07/19 06:00
PHST- 2011/05/25 00:00 [received]
PHST- 2011/07/06 00:00 [accepted]
PHST- 2011/07/19 06:00 [entrez]
PHST- 2011/07/19 06:00 [pubmed]
PHST- 2012/02/22 06:00 [medline]
AID - 10.1007/s11010-011-0984-1 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2011 Dec;358(1-2):335-43. doi: 10.1007/s11010-011-0984-1. Epub 
      2011 Jul 16.