Identification and possible regulation of muscle cell lysosomal protease activity by exogenous protease inhibitors.

Using immunohistochemical or histochemical techniques lysosomal proteases have been localized in muscle cells. These include two exopeptidases (dipeptidyl peptidase I and II) and three endopeptidases (cathepsins B, D, and H). In general, the enzymes varied in apparent activities with the soleus muscle always more reactive than the extensor digitorum longus (EDL) of the rat. Cathepsin B and dipeptidyl peptidase I were localized primarily in subsarcolemmal regions whereas cathepsin H and dipeptidyl peptidase II were scattered throughout the sarcoplasm consistent with other observation of two populations of muscle lysosomes. However, cathepsin D could not be localized in either type of lysosome by similar histochemical techniques. Using immunohistochemical techniques, the protease inhibitors alpha 1-antitrypsin and alpha 1-inhibitor3 were recognized in intracellular compartments within muscle cells. alpha 1-antitrypsin appeared scattered throughout the cytoplasm while alpha 1-inhibitor3 was localized in discrete subsarcolemmal regions. Both inhibitor content and protease activity were diminished in skeletal muscles following streptozotocin-induced diabetes.