Oleic acid induces endothelin-1 expression through activation of protein kinase C and NF-kappa B.
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.
Park
Joong-Yeol
JY
Department of Internal Medicine, University of Ulsan College of Medicine, Poongnap-dong, Songpa-ku, 138-736, Seoul, South Korea
Kim
Yun Mi
YM
Song
Hai Sun
HS
Park
Ki Young
KY
Kim
Young Mi
YM
Kim
Min Seon
MS
Pak
Youngmi Kim
YK
Lee
In Kyu
IK
Lee
Jae Dam
JD
Park
Seung-Jung
SJ
Lee
Ki-Up
KU
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
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