Apoptosis in multinucleated skeletal muscle myotubes

Several recent studies report endonuclease-mediated DNA degradation as evid ence of apoptotic degeneration of skeletal muscle in the muscular dystrophi es and other muscle disorders. Interpretation of the results of such studie s is complicated by the ubiquitous presence of non-muscle cells within musc le in vivo and by a lack of knowledge concerning the nature of the process of apoptosis in postmitotic, multinucleated skeletal muscle and the potenti al mechanisms involved. Staurosporine treatment of C2C12 skeletal muscle my otubes induced several classic features of apoptosis, including cell and nu clear shrinkage with initial preservation of cellular membranes. Externaliz ation of phosphatidylserine occurred within 2 hours of treatment, and myotu bes contained procaspase 3, which seemed to be activated within 4 hours. DN A degradation was identified by transferase uridine triphosphate nick-end l abeling within 4 hours, and DNA ladders were identified on agarose electrop horesis of genomic DNA within 8 hours. Thus, the process of apoptosis in po stmitotic multinucleated skeletal muscle shares many of the characteristics of apoptosis in mononuclear mitotic cells. However, the pattern of degener ation does not seem to be compatible with that seen in the muscular dystrop hies.