Effect of prednisone on protease activities and structural protein levels in rat muscles in vivo

To further elucidate the biochemical mechanism by which the corticosteroid prednisone induces differential changes in muscle mass (via altered protein synthesis/degradation rates) in normal or degenerating muscle tissues, we have determined the activity of a range of proteolytic enzyme types, together with levels of muscle structural proteins, in five innervated and denervated muscle types from control and drug treated rats, In both normal and wasting muscles, the activity of many protease types was substantially down-regulated following treatment with prednisone; however, accompanying net decreases in muscle mass were observed (although the structural protein composition of muscles was unaltered following drug treatment), We conclude that whilst overall rates of protein degradation in both normal and degenerating muscle may be reduced (via protease down-regulation) following prednisone treatment, the effect of the latter in reducing protein synthesis rates must be proportionately greater (even in actively degenerating tissue), Thus, the data do not support the hypothesis that the beneficial effect of prednisone in maintaining muscle mass in pathological tissues (e.g., Duchenne muscular dystrophy (DMD)) operates principally via down-regulation of protease action/protein catabolism.