Phorbol ester treatment inhibits proliferation and differentiation of cultured human skeletal muscle satellite cells by differentially acting on protein kinase C isoforms

We have previously shown that cultured human skeletal muscle cells express five protein kinase C (PKC) isoforms (PKC alpha, -gamma, -eta, -theta, and -zeta) and that expression levels of various PKC isozymes differentially ch ange during differentiation. In this study we investigated the effects of t he PKC activator phorbol 12-myristate 13-acetate (PMA) on differentiation a nd on PKC isozymes of human skeletal muscle satellite cells. PMA inhibited the growth and fusion of cultured human myoblasts in a dose-dependent manne r. In addition, prolonged treatment of cells with PMA suppressed the expres sion of the myogenic differentiation marker desmin showing similar dose-res ponse characteristics. Furthermore, PMA also induced the intracellular tran slocation of PKC gamma, -eta, and -theta, whereas cellular localization of PKC alpha and -zeta were not altered. These changes in subcellular localiza tion patterns were of great importance since only those PKC isoforms were t ranslocated that possessed alterations in their expression levels during di fferentiation. Our findings, therefore, suggest that the PMA-induced inhibi tion of differentiation of human skeletal muscle cells is mediated by certa in PKC isoforms. Moreover, these data strongly argue for differential and i sozyme-specific roles of various PKC isoforms in these processes.