PMID: 14684755Dec 20, 2003Paper

Involvement of CYP 2C9 in mediating the proinflammatory effects of linoleic acid in vascular endothelial cells

Journal of the American College of Nutrition
Saraswathi ViswanathanBernhard Hennig

Abstract

Polyunsaturated fatty acids such as linoleic acid are well known dietary lipids that may be atherogenic by activating vascular endothelial cells. In the liver, fatty acids can be metabolized by cytochrome P450 (CYP) enzymes, but little is known about the role of these enzymes in the vascular endothelium. CYP 2C9 is involved in linoleic acid epoxygenation, and the major product of this reaction is leukotoxin (LTX). We investigated the role of CYP-mediated mechanisms of linoleic acid metabolism in endothelial cell activation by examining the effects of linoleic acid or its oxidized metabolites such as LTX and leukotoxin diol (LTD). The effect of linoleic acid on CYP 2C9 gene expression was studied by RT-PCR. Oxidative stress was monitored by measuring DCF fluorescence and intracellular glutathione levels, and electrophoretic mobility shift assay was carried out to study the activation of oxidative stress sensitive transcription factors. Analysis of oxidized lipids was carried out by liquid chromatography/mass spectrometry. Linoleic acid treatment for six hours increased the expression of CYP 2C9 in endothelial cells. Linoleic acid-mediated increase in oxidative stress and activation of AP-1 were blocked by sulfaphenazole, a speci...Continue Reading

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Related Concepts

LTX, Actinobacillus actinomycetemcomitans
9,10-dihydroxy-12-octadecenoic acid
CYP2C9 protein, human
Xenobiotic Monooxygenases
Dose-Response Relationship, Immunologic
Endothelium, Vascular
Exotoxins
Reduced Glutathione
Immunosuppressive Agents
Chromatography, Gas-Liquid-Mass Spectrometry

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