Expression of epoxygenases belonging to CYP2 family in rat myocardial ischemia/reperfusion injury in vivo

Ying Ao, Ren Xiu Peng, Jing Yang, Bing Hua Wang, John R. Falck, Hong Dan, Ying Hui Liu

Research output: Contribution to journalArticle

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Abstract

Objectives: 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 Pharmacolgy, 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) haxanamide (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, an 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 (15mg/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.

Original languageEnglish (US)
Pages (from-to)23-29
Number of pages7
JournalSaudi Medical Journal
Volume29
Issue number1
StatePublished - Jan 2008

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Myocardial Reperfusion Injury
Reperfusion Injury
Reperfusion
Myocardial Ischemia
Superoxides
Cytochrome P-450 CYP2B1
Gene Expression
Cytochrome P-450 CYP2E1
Myocardial Reperfusion
Acids
Reverse Transcriptase Polymerase Chain Reaction
Confocal Microscopy
Cytochrome P-450 Enzyme System
Isoenzymes
Cytochrome P450 Family 2
China
Myocardium
Ischemia
Enzyme-Linked Immunosorbent Assay
Messenger RNA

ASJC Scopus subject areas

  • Medicine(all)

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Expression of epoxygenases belonging to CYP2 family in rat myocardial ischemia/reperfusion injury in vivo. / Ao, Ying; Peng, Ren Xiu; Yang, Jing; Wang, Bing Hua; Falck, John R.; Dan, Hong; Liu, Ying Hui.

In: Saudi Medical Journal, Vol. 29, No. 1, 01.2008, p. 23-29.

Research output: Contribution to journalArticle

Ao, Ying ; Peng, Ren Xiu ; Yang, Jing ; Wang, Bing Hua ; Falck, John R. ; Dan, Hong ; Liu, Ying Hui. / Expression of epoxygenases belonging to CYP2 family in rat myocardial ischemia/reperfusion injury in vivo. In: Saudi Medical Journal. 2008 ; Vol. 29, No. 1. pp. 23-29.
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abstract = "Objectives: 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 Pharmacolgy, 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) haxanamide (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, an 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 (15mg/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.",
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AU - Dan, Hong

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AB - Objectives: 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 Pharmacolgy, 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) haxanamide (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, an 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 (15mg/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.

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