title: Involvement of Rac GTPase activation in phosphatidylcholine hydroperoxide-induced THP-1 cell adhesion to ICAM-1.
abstract: Increasing evidence indicates that phospholipid oxidation plays important roles in atherosclerosis. Here, we investigated the involvement of Rho-family GTPases inphosphatidylcholine hydroperoxide (PCOOH)-induced THP-1 cell adhesion to ICAM-1. Isoprenoid depletion by fluvastatin and geranylgeranyltransferase inhibition by GGTI-286 suppressed PCOOH-induced cell adhesion to ICAM-1 and F-actin-rich membrane protrusion formation. Pull-down assays demonstrated the activation of Rac1 and Rac2 in PCOOH-treated cells. Pan-Rho-family GTPase inhibitor Clostridium difficile toxin B, Rac-specific inhibitor NSC23776, and RNA interference of the Rac isoforms suppressed the cell adhesion. These findings indicate the involvement of Rac GTPase activation in PCOOH-induced cell adhesion to ICAM-1 via actin reorganization.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Nippon Medical School, Tokyo 113-8603, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Asai
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Okajima
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Nagao
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Teruo
authors.initials: T
authors.lastname: Miyazawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oikawa
mesh_terms: D000199:Actins / Q000378:metabolism; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism* / Q000494:pharmacology; D017368:Protein Prenylation / Q000187:drug effects; D034622:RNA Interference; D020744:rac GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D005229:Fatty Acids, Monounsaturated; C437105:GGTI 286; D007211:Indoles; D010713:Phosphatidylcholines; C057590:phosphatidylcholine hydroperoxide; D018799:Intercellular Adhesion Molecule-1; D000077340:Fluvastatin; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D020744:rac GTP-Binding Proteins; D007930:Leucine