?3 PUFA and membrane microdomains: a new frontier in bioactive lipid research

W.L., David; Seo, Jeongmin; Switzer, Kirsten C.; Fan, Yang; McMurray, David N.; Lupton, Joannè R.; Chapkin, Robert S.

doi:10.1016/j.jnutbio.2004.08.002

Cited by 168 publications

(122 citation statements)

References 64 publications

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“…Because ROS production activates ERK-related pathways (27) polyunsaturated fatty acid chain (29). In addition, DHA might interfere with some ROS-producing enzyme system in the endothelium, because n-3 fatty acids can alter membrane lipid microdomains, such as lipid rafts and caveolae (30), involved in the compartmentalization, modulation, and integration of cell signaling components upstream of NF-B, which are sensitive to hydrogen peroxide (27). NADPH oxidase is the principal source of ROS in the endothelium (18).…”

Section: Discussionmentioning

confidence: 99%

The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCε inhibition

Massaro

Habib

Lubrano

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

200

149

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A high intake of the omega-3 fatty acid docosahexaenoate [docosahexaenoic acid (DHA)] has been associated with systemic antiinflammatory effects and cardiovascular protection. Cyclooxygenase (COX)-2 is responsible for the overproduction of prostaglandins (PG) at inflammatory sites, and its expression is increased in atheroma. We studied the effects of DHA on COX-2 expression and activity in human saphenous vein endothelial cells challenged with proinflammatory stimuli. A ≥24-h exposure to DHA reduced COX-2 expression and activity induced by IL-1, without affecting COX-1 expression. DHA effect depended on the NF-κB-binding site in the COX-2 promoter. EMSAs confirmed that DHA attenuated NF-κB activation. Because MAPK, PKC, and NAD(P)H oxidase all participate in IL-1-mediated COX-2 expression, we also tested whether these enzymes were involved in DHA effects. Western blots showed that DHA blocked nuclear p65 NF-κB subunit translocation by decreasing cytokine-stimulated reactive oxygen species and ERK1/2 activation by effects on both NAD(P)H oxidase and PKCε activities. Finally, to address the question whether DHA itself or DHA-derived products were responsible for these effects, we inhibited the most important enzymes involved in polyunsaturated fatty acid metabolism, showing that 15-lipoxygenase-1 products mediate part of DHA effects. These studies provide a mechanistic basis for antiinflammatory and possibly plaque-stabilizing effects of DHA

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Section: Discussionmentioning

confidence: 99%

The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCε inhibition

Massaro

Habib

Lubrano

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

200

149

View full text Add to dashboard Cite

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“…This can have the secondary effect of changing the microenvironment of transmembrane proteins (e.g., receptors) altering the manner in which they interact with their ligands [22]. Altering membrane FA composition can also affect the ability of membrane-associated proteins to actually associate with the membrane and consequently to interact with other multi-protein complexes involved with cell signaling systems [23].…”

Section: Omega-3 Mechanismsmentioning

confidence: 99%

Omega-3 fatty acids and cardiovascular disease: A case for omega-3 index as a new risk factor

Harris

2007

Pharmacological Research

239

140

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The omega-3 fatty acids (FAs) found in fish and fish oils (eicosapentaenoic and docosahexaenoic acids, EPA and DHA) have been reported to have a variety of beneficial effects in cardiovascular diseases. Ecological and prospective cohort studies as well as randomized, controlled trials have supported the view that the effects of these FAs are clinically-relevant. They operate via several mechanisms, all beginning with the incorporation of EPA and DHA into cell membranes. From here, these omega-3 FA alter membrane physical characteristics and the activity of membrane-bound proteins, and once released by intracellular phospholipases, can interact with ion channels, be converted into a wide variety of bioactive eicosanoids, and serve as ligands for several nuclear transcription factors thereby altering gene expression. In as much as blood levels are a strong reflection of dietary intake, it is proposed that an omega-3 FA biomarker, the omega-3 index (erythrocyte EPA+DHA) be considered at least a marker, if not a risk factor, for coronary heart disease, especially sudden cardiac death. The omega-3 index fulfils many of the requirements for a risk factor including consistent epidemiological evidence, a plausible mechanism of action, a reproducible assay, independence from classical risk factors, modifiability, and most importantly, the demonstration that raising tissue levels will reduce risk for cardiac events. For these and a number of other reasons, the omega-3 index compares very favourably with other risk factors for sudden cardiac death.

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“…Both nÀ6 and nÀ3 PUFAs are a component of phospholipid thus influence the structure and function of the membrane [17]. The membrane of the adipose tissue, liver, muscle and the kidney is rich in nÀ6 PUFAs, whereas that of the brain, testis and of retina contain nÀ3 PUFAs predominantly [18].…”

Section: Introductionmentioning

confidence: 99%

ELOVL2 overexpression enhances triacylglycerol synthesis in 3T3‐L1 and F442A cells

2007

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Elongation of very long-chain fatty acids (ELOVL) members were overexpressed in two preadipocyte cell lines, ELOVL2 and ELOVL3 in 3T3-L1 cells, and ELOVL1-3 in F442A cells. Cells overexpressing ELOVL2, whose preferred substrates are arachidonic acid (AA, C20:4nÀ6) and eicosapentaenoic acid (EPA, C20:5nÀ3), showed an enhanced triacylglycerol (TAG) synthesis and subsequent accumulation of lipid droplets. Incorporation of fatty acid (FA) but not of glucose into TAG was enhanced by ELOVL2-overexpression. Two lipogenic genes encoding diacylglycerol acyltransferase-2 (DGAT2) and fatty acid-binding protein-4 (FABP4, aP2) were induced in ELOVL2-overexpressing cells, whereas no such effect was seen on the fatty acid synthase (FAS) gene.

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?3 PUFA and membrane microdomains: a new frontier in bioactive lipid research

Cited by 168 publications

References 64 publications

The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCε inhibition

The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCε inhibition

Omega-3 fatty acids and cardiovascular disease: A case for omega-3 index as a new risk factor

ELOVL2 overexpression enhances triacylglycerol synthesis in 3T3‐L1 and F442A cells

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