Apoptosis in multinucleated skeletal muscle myotubes

Several recent studies report endonuclease-mediated DNA degradation as evidence of apoptotic degeneration of skeletal muscle in the muscular dystrophies and other muscle disorders. Interpretation of the results of such studies is complicated by the ubiquitous presence of non-muscle cells within muscle in vivo and by a lack of knowledge concerning the nature of the process of apoptosis in postmitotic, multinucleated skeletal muscle and the potential mechanisms involved. Staurosporine treatment of C2C12 skeletal muscle myotubes induced several classic features of apoptosis, including cell and nuclear shrinkage with initial preservation of cellular membranes. Externalization of phosphatidylserine occurred within 2 hours of treatment, and myotubes contained procaspase 3, which seemed to be activated within 4 hours. DNA degradation was identified by transferase uridine triphosphate nick-end labeling within 4 hours, and DNA ladders were identified on agarose electrophoresis of genomic DNA within 8 hours. Thus, the process of apoptosis in postmitotic multinucleated skeletal muscle shares many of the characteristics of apoptosis in mononuclear mitotic cells. However, the pattern of degeneration does not seem to be compatible with that seen in the muscular dystrophies.