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...
Gespeichert in:
Veröffentlicht in: | Prostaglandins, leukotrienes and essential fatty acids leukotrienes and essential fatty acids, 2006-09, Vol.75 (3), p.169-177 |
---|---|
Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
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 |