The effect of n-3 PUFA on eNOS activity and expression in Ea hy 926 cells.
The aim of this study was to evaluate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on NO synthase (eNOS) activation in Ea hy 926 endothelial cells. EPA or DHA (0-80 microM), added to the culture medium during 24h, were dose-dependently incorporated into the cells. In control medium, eNOS activity (evaluated by the citrulline assay) and eNOS phosphorylation on Ser 1177 were correlated. They were increased by 10 microM histamine and prevented by 20 microM lysophosphatidylcholine (LPC). By contrast, EPA or DHA increased basal phosphorylation without affecting eNOS activity in non-stimulated cells, but dose-dependently decreased this activity in histamine-stimulated cells without modifying the phosphorylation level. Furthermore, EPA and DHA did not prevent the deleterious effects of LPC on histamine stimulation. In conclusion, incorporation of EPA and DHA could be deleterious for endothelial cells by deregulating the activation of eNOS and preventing NO liberation.
Gousset-Dupont
Aurélie
A
Université Paris-Sud, UMR1154, Faculté de Pharmacie, 5 avenue J-B Clément, Châtenay-Malabry, F-92296, France; IFR141, INRA, Châtenay-Malabry, France.
Robert
Véronique
V
Grynberg
Alain
A
Lacour
Bernard
B
Tardivel
Sylviane
S
D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects
D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III