| A novel estrogen receptor GPER inhibits mitochondria permeability transition pore opening and protects the heart against ischemia-reperfusion injury. | |
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MedLine Citation:
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PMID: 19880667 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jean Chrisostome Bopassa; Mansoureh Eghbali; Ligia Toro; Enrico Stefani |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-10-30 |
Journal Detail:
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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:
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Created Date: 2009-12-18 Completed Date: 2010-01-05 Revised Date: 2011-07-19 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H16-23 Citation Subset: IM |
Affiliation:
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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 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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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:
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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:
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0/Enzyme Inhibitors; 0/Flavonoids; 0/PD 98059; 0/Protective Agents; 56-65-5/Adenosine Triphosphate; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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