| Myocardial apoptosis and infarction after ischemia/reperfusion are attenuated by kappa-opioid receptor agonist. | |
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MedLine Citation:
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PMID: 19608010 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND AIMS: It remains unclear whether U50488H (a selective kappa-opioid receptor agonist) produces anti-apoptotic effect during ischemia and reperfusion (I/R). Therefore, the effect of U50488H on myocardial apoptosis was investigated in the present study. METHODS: Rats were subjected to 45min coronary artery occlusion and 180min of reperfusion. U50488H (1.5mg/kg IV) was given prior to occlusion. Nor-Binaltorphimine (nor-BNI) (2mg/kg IV), a selective kappa-opioid receptor antagonist, was given 10min prior to U50488H. Cardiac apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay and in situ identification of nuclear DNA fragmentation. RESULTS: The ultrastructure injury of myocardium, myocardial infarct size, and plasma CK and LDH were reduced significantly with administration of U50488H before I/R, whereas the effects of U50488H were abolished by nor-BNI. DNA fragments were visualized by agarose electrophoresis, and clear DNA ladder formation was observed in myocardial tissue from hearts subjected to I/R. Administration of U50488H before ischemia exerted a significant anti-apoptotic effect as evidenced by markedly weaker DNA ladder formation. TUNEL staining showed U50488H treatment before I/R significantly reduced the percentage of apoptotic cells, which was blocked by 5-HD, a mitochondrial k(ATP) channel blocker. In accordance, U50488H treatment significantly inhibited I/R-induced elevated activities of caspase-3 and caspase-9. U50488H also produced an increase in Bcl-2 and a decrease in Bax protein expression in the I/R heart, and the anti-apoptotic effects of U50488H were all blocked by nor-BNI. CONCLUSIONS: U50488H reduces myocardial necrosis and apoptosis after I/R and activation of kappa-opioid receptor may mediate a role in U50488H-induced myocardial protection. |
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Authors:
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Fan Rong; Zhang Peng; Ming-Xiang Ye; Quan-Yu Zhang; Yin Zhao; Shu-Miao Zhang; Hai-Tao Guo; Bi Hui; Yue-Min Wang; Cheng Liang; Chun-Hu Gu; Chen Tao; Qin Cui; Shi-Qiang Yu; Ding-Hua Yi; Jian-Ming Pei |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Archives of medical research Volume: 40 ISSN: 1873-5487 ISO Abbreviation: Arch. Med. Res. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-07-17 Completed Date: 2009-09-28 Revised Date: 2010-05-03 |
Medline Journal Info:
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Nlm Unique ID: 9312706 Medline TA: Arch Med Res Country: United States |
Other Details:
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Languages: eng Pagination: 227-34 Citation Subset: IM |
Affiliation:
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Department of Physiology, National Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Shaanxi Province, PR China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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therapeutic use* Animals Antihypertensive Agents / pharmacology Apoptosis / drug effects* Caspase 3 / drug effects, metabolism Caspase 9 / drug effects, metabolism DNA Fragmentation / drug effects Male Microscopy, Electron, Transmission Myocardial Infarction / etiology, pathology, prevention & control* Myocardium / pathology Naltrexone / analogs & derivatives, pharmacology Narcotic Antagonists / pharmacology Proto-Oncogene Proteins c-bcl-2 / drug effects, metabolism Rats Rats, Sprague-Dawley Receptors, Opioid, kappa / agonists* Reperfusion Injury / complications, drug therapy*, pathology bcl-2-Associated X Protein / drug effects, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Narcotic Antagonists; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptors, Opioid, kappa; 0/bcl-2-Associated X Protein; 105618-26-6/norbinaltorphimine; 16590-41-3/Naltrexone; 67198-13-4/3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9 |
| Comments/Corrections | |
Erratum In:
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Arch Med Res. 2010 Jan;41(1):66 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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