title: Oleic acid induces endothelin-1 expression through activation of protein kinase C and NF-kappa B.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Poongnap-dong, Songpa-ku, 138-736, Seoul, South Korea
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Hai Sun
authors.initials: HS
authors.lastname: Song
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Park
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Min Seon
authors.initials: MS
authors.lastname: Kim
authors.forename: Youngmi Kim
authors.initials: YK
authors.lastname: Pak
authors.forename: In Kyu
authors.initials: IK
authors.lastname: Lee
authors.forename: Jae Dam
authors.initials: JD
authors.lastname: Lee
authors.forename: Seung-Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Ki-Up
authors.initials: KU
authors.lastname: Lee
mesh_terms: D002478:Cells, Cultured; D019332:Endothelin-1 / Q000235:genetics*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D008301:Maleimides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009765:Obesity / Q000097:blood; D019301:Oleic Acid / Q000097:blood / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D019301:Oleic Acid; D011493:Protein Kinase C; C070515:bisindolylmaleimide I