Protein turnover in skeletal muscle. II. Effects of denervation and cortisone on protein catabolism in skeletal muscle.

To determine the mechanism by which denervation leads to atrophy of skeletal muscle, the fate of previously labeled protein was studied in denervated and contralateral control muscles of hypophysectomized rats. To label muscle proteins, a single injection of aH-leucine was given to the animals 2 days prior to section of the sciatic nerve. On subsequent days, the animals received unlabeled leucine and a high protein diet. Protein degradative rates were estimated from the disappearance of radioactivity from muscle proteins. Protein synthetic rates were estimated from the decrease in specific activity of these proteins, caused by the dilution of labeled proteins with newly synthesized (unlabeled) material. Ten days after denervation, atrophic muscles contained less total radioactivity than contralateral controls. This result suggests increased protein degradation. Nevertheless, the specific activity of muscle proteins remained unchanged. Protein synthesis therefore must also have decreased following nerve section. The loss of muscle weight following denervation appeared to be directly proportional to the increase in protein degradation. The increase in catabolism of myofibrillar proteins was especially marked, and this tinding accounts for the relative loss of myofibrillar material in the denervated muscles. Analogous experiments were carried out to determine the mechanisms through which cortisone induces muscle atrophy. Two days after injection of labeled leucine, animals received daily injections of cortisone acetate (10 mg per day) or 0.9% sodium chloride solution. Cortisone caused marked atrophy of the plantaris muscle. Although the hormone decreased appreciably the amount of labeled proteins per muscle, it did not alter their specific activity. Thus cortisone both increased protein degradation and decreased protein synthesis. In contrast to denervatioa atrophy, cortisone-atrophy affected the breakdown of myofibrillar and soluble proteins similarly. Cortisone did not cause appreciable loss of weight of the soleus muscle, in which the hormone did not significantly increase protein degradation. However, upon dener-