Inhibition of basal and deprivation-induced proteolysis by leupeptin and pepstatin in perfused rat liver and heart

Isolated rat livers and hearts were perfused in the presence and absence of insulin and amino acids (or insulin alone) to generate the basal and 2x enhanced rates of intracellular protein degradation, respectively, that are normally demonstrable under these conditions. Additions of the thiol-proteinase inhibitor, leupeptin, to each tissue group inhibited both levels of degradation proportionately. In liver, administration of a pepstatin-liposome complex reduced deprivation-enhanced proteolysis by a small degree (20%), but when added with leupeptin, basal and deprivation rates were inhibited 55-60%. These findings are consistent with the notion that the lysosomal system is involved in both degradative components.