title: The role of Rho/Rho-kinase pathway in the expression of ICAM-1 by linoleic acid in human aortic endothelial cells.
abstract: Linoleic acid (LA), a dietary unsaturated fatty acid, has been known to increase the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) through the activation of nuclear factor-kappa B. Rho/Rho-kinase (ROCK) pathway mediates various cellular functions related to cardiovascular disease and affects the expression of ICAM-1. However, the exact mechanism underlying this action has not been fully elucidated. In this study, we aimed to find out the role of Rho/ROCK pathway in LA-induced ICAM-1 expression in human aortic endothelial cells (HAECs). We found that LA increased ICAM-1 expression and phosphorylation of ROCK and MYPT-1, a distal signal of ROCK. Y-27632, a ROCK inhibitor, suppressed ICAM-1 expression and phosphorylation of MYPT-1 induced by LA. The effect of LA on the increased phosphorylation of MYPT1 and expression of ICAM-1 was abolished by knocking down RhoA and ROCK2 protein level expression using small interfering RNA. LA increased NF-κB DNA-binding activity, which was inhibited with pretreatment with Y-27632. This study suggests that Rho/ROCK pathway plays a role in LA-induced ICAM-1 expression, which is possibly mediated by NF-κB in HAECs.
authors: Department of Internal Medicine, University of Ulsan College of Medicine, Poongnap-dong, Songpa-gu, Seoul 138-736, Republic of Korea.
authors: Chang Hee
authors: CH
authors: Jung
authors: Woo Je
authors: WJ
authors: Lee
authors: Jenie Yoonoo
authors: JY
authors: Hwang
authors: So Mi
authors: SM
authors: Seol
authors: Yun Mi
authors: YM
authors: Kim
authors: Yoo La
authors: YL
authors: Lee
authors: Ji Hyun
authors: JH
authors: Ahn
authors: Joong-Yeol
authors: JY
authors: Park
mesh_terms: D000209:Acute-Phase Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000577:Amides / Q000494:pharmacology; D001011:Aorta / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D019787:Linoleic Acid / Q000494:pharmacology*; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; D000577:Amides; D004268:DNA-Binding Proteins; C573420:ICAM1 protein, human; D016328:NF-kappa B; D011725:Pyridines; D034741:RNA, Small Interfering; C010781:acute-phase protein rho; D018799:Intercellular Adhesion Molecule-1; C108830:Y 27632; D019787:Linoleic Acid; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human