Lipids Why a Diet Rich in Seafood Is Healthy

Nancy R. Gough

Science's STKE, AAAS, Washington, DC 20005, USA

Omega-3 fatty acids, which are found in marine organisms, are known for their beneficial health effects. One mechanism for their antiinflammatory effects is competitive inhibition of the enzymatic activity of cyclooxygenase (COX), which is the rate-limiting enzyme in the biosynthesis of prostaglandins. Massaro et al. report that exposure of endothelial cells to the omega-3 fatty acid docosahexaenoate (DHA) for periods long enough to allow incorporation of this lipid into cellular membranes inhibits the activation of nuclear factor B (NF-B) and subsequently COX-2 expression and prostaglandin production in response to proinflammatory signals. Treatment of human saphenous vein endothelial cells (HSVECs) with DHA for up to 48 hours maximally inhibited COX activation in response to subsequent exposure of the cells to interleukin 1 (IL-1) or a phorbol ester. Western blot and Northern analysis showed that DHA treatment inhibited the IL-1- or phorbol ester-stimulated expression and abundance of COX-2 (the inducible isoform) without affecting that of COX-1 (the constitutively expressed isoform). Reporter gene analysis demonstrated that DHA-mediated inhibition of COX-2 required the NF-B binding site in the COX-2 promoter, and DHA pretreatment decreased IL-1 stimulation of NF-B DNA binding (measured by electrophoretic mobility shift assay) and nuclear translocation (measured by cell fractionation followed by Western blotting). DHA treatment inhibited several steps in the pathway activated by IL-1 that leads to NF-B activation. In cells treated with DHA, subsequent responses to IL-1 showed (i) decreased extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation but no change in activation of p38 mitogen-activated protein kinase (p38 MAPK), (ii) decreased reactive oxygen species production through inhibition of membrane association of the p47^phox subunit of NADPH oxidase, and (iii) decreased membrane association of protein kinase C (PKC) but not PKC or PKC. Thus, it appears that the long-term beneficial effects of omega-3 fatty acids may be due to alteration of membrane lipid composition leading to reduced signaling in response to inflammatory stimuli.

M. Massaro, A. Habib, L. Lubrano, S. Del Turco, G. Lazzerini, T. Bourcier, B. B. Weksler, R. De Caterina, The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKC inhibition. Proc. Natl. Acad. Sci. U.S.A. 103, 15184-15189 (2006). [Abstract] [Full Text]

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