Protein metabolism in unweighting atrophy.

Abstract

The weightless environment results in atrophy of the anti-gravity muscles. Hindlimb suspension is a model for weightlessness induced atrophy. This study evaluated the effects of hindlimb suspension, microgravity and exercise training followed by suspension on skeletal muscle. Soleus mass, myofibrillar and sarcoplasmic protein content were measured in one to four day hindlimb suspended animals. Protein synthesis was measured by intramuscular injection of ³H phenylalanine with correction for the difference between tRNA and intracellular specific activities. Myofibrillar protein loss was minimal after two days of unweighting but significant after three days. Although sarcoplasmic protein content showed no change, synthesis of both protein pools declined in parallel. Myofibrillar degradation increased during the first three days of unweighting, partially accounting for protein loss. The decline in degradation during day four explained the slower rate of protein loss at this time. Sarcoplasmic protein degradation increased slightly during the first two days of unweighting then declined sharply, thus explaining the sparing of sarcoplasmic proteins. Animals exposed to weightlessness showed soleus atrophy similar to suspended animals. The plantaris and gastrocnemius had reduced growth while the extensor digitorum longus and tibialis anterior grew normally in flight and suspended animals. Insulin stimulated glucose uptake was enhanced in soleus, but not extensor digitorum longus of flight and suspended animals. In situ insulin and IGF-1 stimulated 2-deoxyglucose uptake was greater after six days of suspension. Voluntary wheel training increased soleus mass, protein content and in vivo protein synthesis which plateaued by three weeks. Suspended or trained-suspended animals showed reductions in soleus mass, protein content and synthesis compared to trained animals. However, trained-suspended animals showed higher values for protein content and synthesis compared to suspended animals. In conclusion, these studies show that unweighting atrophy is characterized by decreased synthesis and increased degradation of myofibrillar proteins, and a sparing of sarcoplasmic proteins due to slower degradation. Tail-cast hindlimb suspension may be used as a ground based model to mimic the effects of weightlessness on muscle proteins. Wheel training causes muscle hypertrophy; and although training prior to suspension provides some protection against protein loss, it does not prevent atrophy.