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Effects of protein kinase inhibitors on growth factor-stimulated DNA synthesis in cultured rat vascular smooth muscle cells

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      Abstract

      The effects of H-7 and ML-9, inhibitors of protein kinase C and myosin light-chain kinase, respectively, on DNA synthesis stimulated by platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) were studied in cultured rat vascular smooth muscle cells (VSMC). H-7 and ML-9 significantly inhibited PDGF-stimulated DNA synthesis in lower concentrations, while both compounds were only effective in inhibiting EGF-induced DNA synthesis in higher concentrations. These data suggest that protein kinase C and myosin light-chain kinase activated by PDGF play a more important role in cell proliferation of VSMC than EGF.

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      References

        • Ross R.
        • Glomset J.A.
        The pathogenesis of atherosclerosis.
        New. Engl. J. Med. 1976; 295: 420
        • Schwartz S.M.
        Cellular proliferation in atherosclerosis and hypertension.
        Exp. Biol. Med. 1983; 173: 1
        • Vogel A.
        • Ravies E.
        • Kariya B.
        • Rivest M.J.
        • Ross R.
        Coordinate control of 3T3 cell proliferation by platelet-derived growth factor and plasma component.
        in: Proc. Natl. Acad. Sci. USA. 75. 1978: 28110
        • Tomita M.
        • Hirata Y.
        • Uchihashi M.
        • Fujita T.
        Characterization of epidermal growth factor receptors in cultured vascular smooth muscle cells of rat aorta.
        Endocrinol. Jap. 1986; 33: 177
        • Kariya K.
        • Kawahara Y.
        • Tsuda T.
        • Fukusaki H.
        • Takai Y.
        Possible involvement of protein kinase C in platelet derived growth factor-stimulated DNA synthesis in vascular smooth muscle cells.
        Atherosclerosis. 1987; 63: 251
        • Tanaka T.
        • Ohmura T.
        • Yamakado T.
        • Hidaka H.
        Two types of calcium-dependent protein phosphorylation modulated by calmodulin antagonist.
        Mol. Pharmacol. 1982; 22: 408
        • Berridge M.J.
        • Irvine R.F.
        Inositol triphosphate a novel second messenger in cellular signal transduction.
        Nature. 1984; 312: 315
        • Nishizuka Y.
        Studies and perspectives of protein kinase C.
        Science. 1986; 233: 305
        • Williams L.T.
        • Tremble P.
        • Antoniades H.N.
        Platelet-derived growth factor binds specifically to receptors on vascular smooth muscle cells and the binding becomes nondissociable.
        in: Proc. Natl. Acad. Sci. USA. 79. 1982: 5867
        • Shechter Y.
        • Hernaez L.
        • Cuatrecasas P.
        Epidermal growth factor: biological activity requires persistent occupation of high-affinity cell surface receptors.
        in: Proc. Natl. Acad. Sci. USA. 75. 1978: 5788
        • Hidaka H.
        • Inagaki M.
        • Kawamoto S.
        • Sasaki Y.
        Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C.
        Biochemistry. 1984; 23: 5036
        • Saitoh M.
        • Naka M.
        • Hidaka H.
        The modulatory role of myosin light chain phosphorylation in human platelet activation.
        Biochem. Biophys. Res. Commun. 1986; 140: 280
        • Ross R.
        The smooth muscle cell, II. Growth of smooth muscle cell in culture and formation of elastic fibers.
        J. Cell. Biol. 1971; 50: 172
        • Hidaka M.
        • Sasaki Y.
        • Tanaka Y.
        • Endo T.
        • Ohno S.
        • Fujii Y.
        • Nagato T.
        N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide, a calmodulin antagonist inhibits cell proliferation.
        in: Proc. Natl. Acad. Sci. USA. 78. 1981: 4354
        • Ives H.E.
        • Daniel T.O.
        Interrelationship between growth factor-induced pH changes and intracellular Cab+.
        in: Proc. Natl. Acad. Sci. USA. 84. 1987: 1950
        • Tomita M.
        • Hirata Y.
        • Takata S.
        • Fujita T.
        Effects of calcium-antagonists and calmodulin inhibitors on DNA synthesis in cultured rat vascular smooth muscle cells.
        Endocrinol. Jap. 1987; 34: 313
        • Clark R.B.
        • Love J.T.
        • Sgroi D.
        • Lingenheld E.G.
        • Sha'afi R.I.
        The protein kinase C inhibitor, H-7, inhibits antigen and IL-2-induced proliferation of murine T cell lines.
        Biochem. Biophys. Res. Commun. 1987; 145: 666
        • Kaibuchi K.
        • Tsuda T.
        • Kikuchi A.
        • Tanimoto T.
        • Yamashita T.
        • Takai Y.
        Possible involvement of protein kinase C and calcium ion in growth factor-induced expression of c-myc oncogene in Swiss 3T3.
        J. Biol. Chem. 1986; 261: 1187
        • Tsuda T.
        • Hamamori Y.
        • Fukumoto Y.
        • Kaibuchi K.
        • Takai Y.
        Epidermal growth factor increases c-myc mRNA without eliciting phosphoinositide turnover, protein kinase C activation, or calcium ion mobilization in Swiss 3T3 Fibroblasts.
        J. Biochem. 1986; 100: 1631