| Autor: |
Harmon, Shawn D., Fang, Xiang, Kaduce, Terry L., Hu, Shanming, Raj Gopal, V., Falck, John R., Spector, Arthur A. |
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| Zdroj: |
Prostaglandins Leukotrienes & Essential Fatty Acids; Sep2006, Vol. 75 Issue 3, p169-177, 9p |
| Abstrakt: |
Abstract: 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 0.5–5μM EPA, DHA or ω-3 docosapentaenoic acid (DPA) to incubations containing 0.5μM [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. [Copyright &y& Elsevier] |
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