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| Content Provider | Springer Nature Link |
|---|---|
| Author | El Sherbeni, Ahmed A. Aboutabl, Mona E. Zordoky, Beshay N. M. Anwar Mohamed, Anwar El Kadi, Ayman O. S. |
| Copyright Year | 2012 |
| Abstract | Cytochrome P450 (P450)-derived arachidonic acid (AA) metabolites serve pivotal physiological roles. Therefore, it is important to determine the dominant P450 AA monooxygenases in different organs. We investigated the P450 AA monooxygenases protein expression as well as regioselectivity, immunoinhibition, and kinetic profile of AA epoxygenation and hydroxylation in rat heart, lung, kidney, and liver. Thereafter, the predominant P450 epoxygenases and P450 hydroxylases in these organs were characterized. Microsomes from heart, lung, kidney, and liver were incubated with AA. The protein expression of CYP2B1/2, CYP2C11, CYP2C23, CYP2J3, CYP4A1/2/3, and CYP4Fs in the heart, lung, kidney, and liver were determined by Western blot analysis. The levels of AA metabolites were determined by liquid chromatography–electrospray ionization mass spectroscopy. This was followed by determination of regioselectivity, immunoinhibition effect, and the kinetic profile of AA metabolism. AA was metabolized to epoxyeicosatrienoic acids and 19- and 20-hydroxyeicosatetraenoic acid in the heart, lung, kidney, and liver but with varying metabolic activities and regioselectivity. Anti-P450 antibodies were found to differentially inhibit AA epoxygenation and hydroxylation in these organs. Our data suggest that the predominant epoxygenases are CYP2C11, CYP2B1, CYP2C23, and CYP2C11/CYP2C23 for the heart, lung, kidney, and liver, respectively. On the other hand, CYP4A1 is the major ω-hydroxylase in the heart and kidney; whereas CYP4A2 and/or CYP4F1/4 are probably the major hydroxlases in the lung and liver. These results provide important insights into the activities of P450 epoxygenases and P450 hydroxylases-mediated AA metabolism in different organs and their associated P450 protein levels. |
| Starting Page | 112 |
| Ending Page | 122 |
| Page Count | 11 |
| File Format | |
| ISSN | 12341234 |
| Journal | The AAPS Journal |
| Volume Number | 15 |
| Issue Number | 1 |
| e-ISSN | 15507416 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2012-11-10 |
| Publisher Institution | American Association of Pharmaceutical Scientists |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | arachidonic acid metabolism cytochrome P450 kinetics P450 epoxygenase activity P450 hydroxylase activity regioselectivity Pharmacology/Toxicology Biochemistry Biotechnology Pharmacy |
| Content Type | Text |
| Resource Type | Article |
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