Protein tyrosine kinase inhibitors inhibit chemotaxis of vascular smooth muscle cells

Kentaro Shimokado, Tasuku Yokota, Kazuo Umezawa, Toshiyuki Sasaguri, Jun Ogata

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The effects of protein tyrosine kinase inhibitors on platelet-derived growth factor (PDGF)-induced chemotaxis in cultured rat aortic smooth muscle cells (SMCs) were investigated to elucidate the role of tyrosine phosphorylation in the chemotaxis of vascular SMCs. Two tyrosine kinase inhibitors, methyl 2,5-dihydroxycinnamate and genistein, inhibited PDGF-induced chejnotaxis, the IC50 being 5 and 150 μmol/L, respectively. Methyl cinnamate and genistein partly inhibited the adhesion of SMC to collagen-coated dishes. A chemotaxis assay using double-well culture dishes revealed that both agents also inhibited cell migration after adhesion. H-7, a C kinase inhibitor, did not inhibit either chemotaxis or SMC adhesion at 100 μmol/L. Western blot analysis using anti-phosphotyrosine revealed that the tyrosine kinase inhibitors inhibited the tyrosine phosphorylation of at least two proteins of molecular weight 85 and 95 kD under our experimental conditions. An immunocytochemical study revealed that these inhibitors eliminated tyrosine phosphorylation along the cell margins; these agents also inhibited the reorganization of microtubules and stress fibers, both of which are involved in directional cell locomotion. These findings suggest that tyrosine kinases may play an important role in SMC chemotaxis.

Original languageEnglish
Pages (from-to)973-981
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Volume14
Issue number6
DOIs
Publication statusPublished - Jan 1 1994
Externally publishedYes

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Chemotaxis
Protein Kinase Inhibitors
Vascular Smooth Muscle
Protein-Tyrosine Kinases
Smooth Muscle Myocytes
Tyrosine
Genistein
Platelet-Derived Growth Factor
Phosphorylation
Cell Movement
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Stress Fibers
Phosphotyrosine
Cell Adhesion
Microtubules
Inhibitory Concentration 50
Phosphotransferases
Collagen
Molecular Weight
Western Blotting

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Protein tyrosine kinase inhibitors inhibit chemotaxis of vascular smooth muscle cells. / Shimokado, Kentaro; Yokota, Tasuku; Umezawa, Kazuo; Sasaguri, Toshiyuki; Ogata, Jun.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 14, No. 6, 01.01.1994, p. 973-981.

Research output: Contribution to journalArticle

Shimokado, Kentaro ; Yokota, Tasuku ; Umezawa, Kazuo ; Sasaguri, Toshiyuki ; Ogata, Jun. / Protein tyrosine kinase inhibitors inhibit chemotaxis of vascular smooth muscle cells. In: Arteriosclerosis, thrombosis, and vascular biology. 1994 ; Vol. 14, No. 6. pp. 973-981.
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