Oxygenation of ω-3 fatty acids by human cytochrome P450 4F3B: Effect on 20-hydroxyeicosatetraenoic acid production

Cytochrome P450 (CYP) ω-oxidases convert arachidonic acid (AA) to 20-hydroxyeicosatetraenoic acid (20-HETE), a lipid mediator that modulates vascular tone. We observed that a microsomal preparation containing recombinant human CYP4F3B, which converts AA to 20-HETE, converted eicosapentaenoic acid (E...

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Veröffentlicht in:Prostaglandins, leukotrienes and essential fatty acids leukotrienes and essential fatty acids, 2006-09, Vol.75 (3), p.169-177
Hauptverfasser: Harmon, Shawn D., Fang, Xiang, Kaduce, Terry L., Hu, Shanming, Raj Gopal, V., Falck, John R., Spector, Arthur A.
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Sprache:eng
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Zusammenfassung:Cytochrome P450 (CYP) ω-oxidases convert arachidonic acid (AA) to 20-hydroxyeicosatetraenoic acid (20-HETE), a lipid mediator that modulates vascular tone. We observed that a microsomal preparation containing recombinant human CYP4F3B, which converts AA to 20-HETE, converted eicosapentaenoic acid (EPA) to 20-OH-EPA. Likewise, docosahexaenoic acid (DHA) was converted to 22-OH-DHA, indicating that human CYP4F3B also can oxidize 22-carbon ω-3 fatty acids. Consistent with these findings, addition of 0.5–5 μM EPA, DHA or ω-3 docosapentaenoic acid (DPA) to incubations containing 0.5 μM [ 3H]AA inhibited [ 3H]20-HETE production by 15–65%. [ 3H]20-OH-EPA was rapidly taken up by COS-7 cells, and almost all of the incorporated radioactivity remained as unmodified 20-OH-EPA. The 20-OH-EPA stimulated luciferase activity in COS-7 cells that express peroxisome proliferator-activated receptor α, indicating that this EPA metabolite may function as a lipid mediator. These findings suggest that some functional effects of ω-3 fatty acid supplementation may be due to inhibition of 20-HETE formation or the conversion of EPA to the corresponding ω-oxidized product.
ISSN:0952-3278
1532-2823
DOI:10.1016/j.plefa.2006.05.005