Document Detail


Expression of epoxygenases belonging to CYP2 family in rat myocardial ischemia/reperfusion injury in vivo.
MedLine Citation:
PMID:  18176666     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To elucidate the expression of epoxygenases belonging to cytochrome P-450 mono-oxygenases (CYP2) family in rat ischemic myocardium at varying reperfusion periods, and the effect of epoxygenase inhibition on the post-ischemic heart. METHODS: The current study was conducted in the Department of Pharmacology, Medical College of Wuhan University, China, between September 2004 and June 2005. Rats were subjected to 40 minutes of myocardial ischemia, followed by 0, 15, 60, and 180 minutes of reperfusion. Superoxide generation was assayed by confocal microscopy, CYP2B1/2, 2C6, 2E1, 2J3 gene expressions were determined by reverse transcriptase polymerase chain reaction. Fourteen, 15-dihydroxyeicosatrienoic acid (DHET) concentration was measured by enzyme-linked immunosorbent assay. The effects of the CYP epoxygenase inhibitor N-methylsulphonyl-6-(2-propargyloxyphenyl) hexanamide (MS-PPOH) on myocardial damage and superoxide generation caused by 60 minutes of reperfusion were also evaluated. RESULTS: During myocardial ischemia/reperfusion, CYP2C6 and 2J3 mRNA expression were up-regulated with the peak level at 15 minutes of reperfusion; CYP2E1 gene expression decreased in a time dependent manner and reached the minimum level at 180 minutes of post-ischemia. Meanwhile, no obvious variations of CYP2B1/2 gene expression were detected during different reperfusion periods. Fourteen, 15-DHET significantly increased during reperfusion in ischemic hearts. The MS-PPOH pretreatment (15 mg/kg) effectively reduced myocardial damage and superoxide production. CONCLUSION: There are changes in gene expression of individual isozymes and an elevation of CYP epoxygenase activity involved in myocardial reperfusion injury in vivo. Epoxygenase inhibition plays a protective role in cardiac post-ischemic damage.
Authors:
Ying Ao; Ren-Xiu Peng; Jing Yang; Bing-Hua Wang; John R Falck; Hong Dan; Ying-Hui Liu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Saudi medical journal     Volume:  29     ISSN:  0379-5284     ISO Abbreviation:  Saudi Med J     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-07     Completed Date:  2008-03-25     Revised Date:  2008-06-23    
Medline Journal Info:
Nlm Unique ID:  7909441     Medline TA:  Saudi Med J     Country:  Saudi Arabia    
Other Details:
Languages:  eng     Pagination:  23-9     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Medical College of Wuhan University, Wuhan, China.
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MeSH Terms
Descriptor/Qualifier:
Amides / pharmacology
Analysis of Variance
Animals
Creatine Kinase / blood
Cytochrome P-450 Enzyme System / metabolism*
Enzyme-Linked Immunosorbent Assay
Gene Expression
L-Lactate Dehydrogenase / blood
Male
Malondialdehyde / blood
Myocardial Ischemia / enzymology*
Myocardial Reperfusion Injury / blood,  enzymology*,  prevention & control
Oxidoreductases / metabolism*
Random Allocation
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Superoxides / metabolism
Up-Regulation
Grant Support
ID/Acronym/Agency:
GM31278/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Amides; 0/N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide; 11062-77-4/Superoxides; 542-78-9/Malondialdehyde; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Oxidoreductases; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 1.14.14.1/CYP2B12 protein, rat; EC 2.7.3.2/Creatine Kinase

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