Document Detail


A novel estrogen receptor GPER inhibits mitochondria permeability transition pore opening and protects the heart against ischemia-reperfusion injury.
MedLine Citation:
PMID:  19880667     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several studies have recently demonstrated that G protein-coupled receptor 30 (GPER) can directly bind to estrogen and mediate its action. We investigated the role and the mechanism of estrogen-induced cardioprotection after ischemia-reperfusion using a specific GPER agonist G1. Isolated hearts from male mice were perfused using Langendorff technique with oxygenated (95% O(2) and 5% CO(2)) Krebs Henseleit buffer (control), with G1 (1 microM), and G1 (1 microM) together with extracellular signal-regulated kinase (Erk) inhibitor PD-98059 (5 microM). After 20 min of perfusion, hearts were subjected to 20 min global normothermic (37 degrees C) ischemia followed by 40 min reperfusion. Cardiac function was measured, and myocardial necrosis was evaluated by triphenyltetrazolium chloride staining at the end of the reperfusion. Mitochondria were isolated after 10 min of reperfusion to assess the Ca(2+) load required to induce mitochondria permeability transition pore (mPTP) opening. G1-treated hearts developed better functional recovery with higher rate pressure product (RPP, 6140 +/- 264 vs. 2,640 +/- 334 beats mmHg(-1) min(-1), P < 0.05). The infarct size decreased significantly in G1-treated hearts (21 +/- 2 vs. 46 +/- 3%, P < 0.001), and the Ca(2+) load required to induce mPTP opening increased (2.4 +/- 0.06 vs. 1.6 +/- 0.11 microM/mg mitochondrial protein, P < 0.05) compared with the controls. The protective effect of G1 was abolished in the presence of PD-98059 [RPP: 4,120 +/- 46 beats mmHg(-1) min(-1), infarct size: 53 +/- 2%, and Ca(2+) retention capacity: 1.4 +/- 0.11 microM/mg mitochondrial protein (P < 0.05)]. These results suggest that GPER activation provides a cardioprotective effect after ischemia-reperfusion by inhibiting the mPTP opening, and this effect is mediated by the Erk pathway.
Authors:
Jean Chrisostome Bopassa; Mansoureh Eghbali; Ligia Toro; Enrico Stefani
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-10-30
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  298     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-18     Completed Date:  2010-01-05     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H16-23     Citation Subset:  IM    
Affiliation:
Division of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-7115, USA. jcbopassa@ucla.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / physiology
Animals
Blotting, Western
Enzyme Inhibitors / therapeutic use
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors,  physiology
Flavonoids / therapeutic use
Heart Diseases / prevention & control
Hemodynamics / physiology
Male
Mice
Mice, Inbred C57BL
Mitochondria, Heart / physiology*
Myocardial Infarction / pathology
Myocardium / pathology*
Oxidative Stress / physiology
Permeability
Protective Agents
Reperfusion Injury / pathology*
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
HL-080111/HL/NHLBI NIH HHS; HL-088640/HL/NHLBI NIH HHS; HL-089876/HL/NHLBI NIH HHS; HL-54970/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Enzyme Inhibitors; 0/Flavonoids; 0/Protective Agents; 56-65-5/Adenosine Triphosphate; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases
Comments/Corrections

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