Differential signaling through NFkappaB does not ameliorate skeletal myoblast apoptosis during differentiation.
During 23A2 skeletal myoblast differentiation, roughly 30% of the population undergoes apoptosis. Further, constitutive signaling by G12V:H-Ras or Raf:CAAX abrogates this apoptosis. In this study, we demonstrate an increase in NFkappaB activity in myoblasts that have survived and are expressing muscle-specific genes. NFkappaB activity is also elevated in myoblasts expressing constitutively active G12V:H-Ras but not Raf:CAAX. Expression of a dominant negative IkappaB (IkappaB-SR) sufficient to eliminate this elevated level of NFkappaB activity, in either the 23A2 myoblasts or their G12V:H-Ras-expressing counterparts, however, does not affect survival. Furthermore, expression of a constitutively active IkappaB kinase in 23A2 myoblasts does not protect these cells from the apoptosis associated with differentiation. Since signaling by IkappaB kinase can abrogate differentiation, this result demonstrates that abrogated differentiation and abrogated apoptosis are separable phenotypes.
Dee
Keith
K
Department of Biological, Geological, and Environmental Sciences, 2121 Euclid Avenue, Cleveland State University, Cleveland, OH 44115, USA.
DeChant
Anne
A
Weyman
Crystal M
CM
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D011905:Genes, ras / Q000502:physiology; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction
D016328:NF-kappa B