Effect of radiation on satellite cell activity and protein expression in overloaded mammalian skeletal muscle

Background: To gain insight into the role of satellite cells in skeletal muscle hypertrophy, the effect of radiation on small fiber formation, embryonic myosin heavy chain (embryonic MHC) production, and insulin-like growth factor I (IGF-I) production in overloaded adult rat soleus muscle was examined. Methods: Adult rat soleus muscle was overloaded by ablation of the synergistic gastrocnemius, plantaris, and flexor digitorum profundus muscles of the right hindlimb. Half of the rats were subjected to gamma irradiation of the right hindlimb prior to ablation in an attempt to prevent satellite cell proliferation. Results: Wet weight of the non-irradiated overloaded soleus muscle increased almost 40% compared to contralateral control muscle following 4 weeks of overload. Small fibers, which were rare in control muscle, accounted for 6.76±5.08% to 12.74±7.76% of the total fiber number of the non-irradiated soleus following 1 to 4 weeks of overload. Although usually absent in control muscle, IGF-I or embryonic MHC was immunolocalized in a small percentage (<11%) of the mature fibers in the non-irradiated overloaded soleus. Irradiation prevented compensatory hypertrophy and nearly abolished small fiber formation in the overloaded soleus. However, irradiation did not diminish the percentage of mature fibers producing immunocytochemically detectable levels of embryonic MHC or IGF-I. Conclusions: Irradiation may prevent hypertrophy by impairing activation, proliferation, and/or differentiation of satellite cells. Small fibers in overloaded muscle appear to be new fibers arising from satellite cells. IGF- I may have a role in muscle hypertrophy involving satellite cell activation, or perhaps a more direct role that requires additional factors.