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 (PKCalpha, -gamma, -eta, -theta, and -zeta) and that expression levels of various PKC isozymes differentially change during differentiation. In this study we investigated the effects of the PKC activator phorbol 12-myristate 13-acetate (PMA) on differentiation and on PKC isozymes of human skeletal muscle satellite cells. PMA inhibited the growth and fusion of cultured human myoblasts in a dose-dependent manner. In addition, prolonged treatment of cells with PMA suppressed the expression of the myogenic differentiation marker desmin showing similar dose-response characteristics. Furthermore, PMA also induced the intracellular translocation of PKCgamma, -eta, and -theta, whereas cellular localization of PKCalpha and -zeta were not altered. These changes in subcellular localization patterns were of great importance since only those PKC isoforms were translocated that possessed alterations in their expression levels during differentiation. Our findings, therefore, suggest that the PMA-induced inhibition of differentiation of human skeletal muscle cells is mediated by certain PKC isoforms. Moreover, these data strongly argue for differential and isozyme-specific roles of various PKC isoforms in these processes.
Boczán
J
J
Department of Physiology and Cell Physiology Research Group of the Hungarian Academy of Sciences, University of Debrecen, Medical and Health Science Center, Medical School.
Bíró
T
T
Czifra
G
G
Lázár
J
J
Papp
H
H
Bárdos
H
H
Adány
R
R
Mechler
F
F
Kovács
L
L
D001692:Biological Transport / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003893:Desmin / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D003893:Desmin; D007527:Isoenzymes; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate