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Biochem Biophys Res Commun. 2003 Apr 11;303(3):891-5.
Oleic acid induces endothelin-1 expression through activation of protein kinase C and NF-kappa B.
Park JY, Kim YM, Song HS, Park KY, Kim YM, Kim MS, Pak YK, Lee IK, Lee JD, Park SJ, Lee KU.
Department of Internal Medicine, University of Ulsan College of Medicine, Poongnap-dong, Songpa-ku, 138-736, Seoul, South Korea
This study investigated the effect of oleic acid on the expression levels of endothelin-1 (ET-1) and on the signaling pathways mediating it in human aortic endothelial cells (HAECs). ET-1 mRNA expression was significantly increased by oleic acid in a dose- and time-dependent manner. Elevation of ET-1 expression in response to oleic acid was inhibited by the protein kinase C (PKC) inhibitor, GF109203X, or the NF-kappa B inhibitor, pyrrolidine dithiocarbamate. In addition, both PKC and NF-kappa B activities were significantly increased by oleic acid. Immunoblot analysis revealed that conventional PKCs (PKC-alpha and -beta II isoforms) were significantly increased in the membranous fractions of HAECs treated with oleic acid. PKC inhibitor completely abolished oleic acid-induced NF-kappa B activation, suggesting that PKC activation is upstream of NF-kappa B activation in oleic acid-induced ET-1 expression. These data suggest that elevated plasma oleic acid levels observed in obese, insulin-resistant subjects result in endothelial dysfunction, at least in part, through an increase in ET-1 expression.
PMID: 12670494 [PubMed - indexed for MEDLINE]
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