Manumycin A, inhibitor of ras farnesyltransferase, inhibits proliferation and migration of rat vascular smooth muscle cells

Hirosuke Kouchi*, Kazufumi Nakamura, Kazuo Fushimi, Masakiyo Sakaguchi, Masahiro Miyazaki, Tohru Ohe, Masayoshi Namba

*Corresponding author for this work

Research output: Contribution to journalArticle

43 Scopus citations

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 α actin fibers, as shown by immnofluorecence staining. These results indicate that the interruption of the ras/MAPK signal transduction pathway and the disorganization of α actin fibers are the main cause of manumycin A inhibition of VSMC proliferation and migration induced by PDGF.

Original languageEnglish (US)
Pages (from-to)915-920
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume264
Issue number3
DOIs
StatePublished - Nov 2 1999

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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