Eicosapentaenoic and docosahexaenoic acids reduce PGH synthase 1 expression in bovine aortic endothelial cells.
To enlighten the mechanism of inhibition of prostacyclin (PGI2) production by n-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, cultured endothelial cells were incubated with albumin bound-EPA or -DHA for 22 h. Under these conditions, PGI2 formation in response to bradykinin, calcium ionophore or exogenous arachidonic acid was equally inhibited by 50%, suggesting that the inhibition might occur downstream the phospholipase step, likely at the level of PGH synthase and/or PGI2 synthase activities. Western blot analysis indicated that the mass of the constitutive isoform of PGH synthase (PGH synthase 1), but not PGI2 synthase, was significantly reduced in n-3 fatty acid-enriched cells. In subsequent experiments, PGH synthase 1 mRNA level, measured by northern blotting, was also decreased in n-3 supplemented cells. This reduction was not due to mRNA destabilization. None of these parameters were altered by similar enrichment with oleic acid (OA). These results suggest that EPA and DHA may affect PGH synthase 1 expression, presumably at the transcriptional level.
Achard
F
F
INSERM U352, Biochimie et Pharmacologie INSA-Lyon, Villeurbanne, France.
Gilbert
M
M
Bénistant
C
C
Ben Slama
S
S
DeWitt
D L
DL
Smith
W L
WL
Lagarde
M
M
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects*; D002417:Cattle; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D011464:Epoprostenol / Q000096:biosynthesis; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
D007527:Isoenzymes; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D003577:Cytochrome P-450 Enzyme System; D015118:Eicosapentaenoic Acid; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase