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Mediation of dopamine D2 receptors activation in post-conditioning-attenuated cardiomyocyte apoptosis.
- Source :
-
Experimental cell research [Exp Cell Res] 2014 Apr 15; Vol. 323 (1), pp. 118-130. Date of Electronic Publication: 2014 Jan 09. - Publication Year :
- 2014
-
Abstract
- The physiological and pathological roles of dopamine D2 receptors (DR2) in the regulation of cardiovacular functions have been recognized. DR2 activation protects hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and apoptosis, and ischemic post-conditioning (PC) plays a critical role in cardioprotection as well; however the involvement of the DR2 activation in the PC-induced cardioprotection is unknown. In the present study, we found that the H/R increased the expressions of DR2 mRNA and protein in cardiomyocytes, which were significantly enhanced by PC. Bromocriptine (Bro, a DR2 agonist) further increased DR2 expression, but Haloperidol (Hal, a DR2 antagonist) reversed the Bro-induced DR2 expressions. PC protected against H/R-induced apoptosis, the rise of [Ca(2+)]i, the expressions of cleaved caspase-3 and -9, release of cytochrome c, and mPTP opening. In addition, PC counteracted the reduction of cell viability caused by H/R, increased the phosphorylation of ERK1/2, PI3K, Akt, GSK-3β and mitochondrial membrane potential. PC further increased Bcl-2 expression, promoted PKC-ε translocation to cell membrane, and activated the mitochondrial ATP-sensitive K channels (mKATP). Bro further enhanced the cardioprotective roles of PC, but Hal reversed these effects of Bro. Meanwhile, we found that DR2 was expressed in cell membrane and interacted with PKC-ε in PC. In conclusion, these results suggest that PC attenuates cardiomyocyte apoptosis via inhibition of mPTP opening by DR2-mediated activation of ERK1/2, PI3K-Akt-GSK-3β and PKC-ε-mKATP. These findings provide a novel target for the treatment of ischemic cardiomyopathy.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Apoptosis drug effects
Bromocriptine pharmacology
Calcium metabolism
Cardiotonic Agents
Caspase 3 metabolism
Caspase 9 metabolism
Cell Hypoxia
Cell Survival
Cytochromes c metabolism
Dopamine Agonists pharmacology
Dopamine Antagonists pharmacology
Extracellular Signal-Regulated MAP Kinases metabolism
Glycogen Synthase Kinase 3 metabolism
Glycogen Synthase Kinase 3 beta
Haloperidol pharmacology
KATP Channels metabolism
Membrane Potential, Mitochondrial physiology
Mitochondrial Membrane Transport Proteins metabolism
Mitochondrial Permeability Transition Pore
Myocardial Ischemia drug therapy
Myocytes, Cardiac cytology
Phosphatidylinositol 3-Kinases metabolism
Phosphorylation
Protein Kinase C-epsilon metabolism
Protein Transport physiology
Proto-Oncogene Proteins c-akt metabolism
Proto-Oncogene Proteins c-bcl-2 biosynthesis
RNA, Messenger biosynthesis
Rats
Rats, Wistar
Receptors, Dopamine D2 biosynthesis
Receptors, Dopamine D2 genetics
Signal Transduction drug effects
Signal Transduction physiology
Ischemic Postconditioning
Myocardial Ischemia metabolism
Myocytes, Cardiac metabolism
Receptors, Dopamine D2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2422
- Volume :
- 323
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 24412422
- Full Text :
- https://doi.org/10.1016/j.yexcr.2013.12.028