EFFECTS OF PHORBOL 12-MYRISTATE 13-ACETATE ON THE DIFFERENTIATION PROGRAM OF EMBRYONIC CHICK SKELETAL MYOBLASTS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (6) , 2780-2789
Abstract
The effects of phorbol 12-myristate 13-acetate (PMA) on 3 aspects of myogenesis were analyzed: fusion of mononucleated myogenic cells to form myotubes; synthesis and accumulation of 2 muscle-specific proteins; and DNA synthesis. Using autoradiography combined with immunofluorescent localization of muscle-specific light meromyosin and the muscle-specific intermediate filament protein desmin, embryonic chick myogenic cells cultured in the presence of PMA (50 nM) initiate the synthesis of both desmin and muscle-specific light meromyosin and, by these criteria partially differentiate. These cells differ from normal definitive postmitotic myoblasts, however, since they do not fuse; do not assemble normal myofibrils; and incorporate [3H]thymidine. PMA does not appear to induce DNA synthesis in postmitotic myoblasts, but it apparently permits cells to initiate expression of muscle-specific proteins while preventing complete withdrawal from the cell cycle. Inhibition of fusion by PMA has been reported, but continued incorporation of [3H]thymidine in nuclei of cells expressing muscle-specific proteins is a previously undescribed effect of PMA. This effect is not achieved by 4-.alpha.-phorbol-12,13-didecanoate, a nonpromoting phorbol ester, and may be relevant to the action of PMA as a tumor promoter.