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.
|Original language||English (US)|
|Number of pages||9|
|Journal||Prostaglandins Leukotrienes and Essential Fatty Acids|
|State||Published - Sep 1 2006|
ASJC Scopus subject areas
- Clinical Biochemistry
- Cell Biology