title: Manumycin A, inhibitor of ras farnesyltransferase, inhibits proliferation and migration of rat vascular smooth muscle cells.
abstract: Restenosis after angioplasty is thought to be caused by proliferation and migration of vascular smooth muscle cells (VSMCs), and it is a most serious problem in medical treatment. A low dose (50 ng/ml) of manumycin A, an inhibitor of p21(ras) (ras) farnesylation, significantly inhibited proliferation of rat VSMCs stimulated by the platelet-derived growth factor (PDGF). The mitoinhibitory effect of manumycin A was dose- and time-dependent but was independent of cell density. Western blot analysis showed that manumycin A reduced the amount of functional ras localized at the cytoplasmic membrane and inhibited the phosphorylation of p42/44 mitogen-activated protein kinase (MAPK). Manumycin A also inhibited VSMC migration and disorganized alpha actin fibers, as shown by immnofluorecence staining. These results indicate that the interruption of the ras/MAPK signal transduction pathway and the disorganization of alpha actin fibers are the main cause of manumycin A inhibition of VSMC proliferation and migration induced by PDGF.
authors.affiliation: Department of Cardiovascular Medicine, Institute of Molecular and Cellular Biology, Okayama University Medical School, Okayama, Japan. j-26946@icity.or.jp
authors.forename: H
authors.initials: H
authors.lastname: Kouchi
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Fushimi
authors.forename: M
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: T
authors.initials: T
authors.lastname: Ohe
authors.forename: M
authors.initials: M
authors.lastname: Namba
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D011090:Polyenes / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides; D051381:Rats; D011921:Rats, Inbred WKY; D018631:ras Proteins / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D018631:ras Proteins; C054474:manumycin