Regulation of protein breakdown in hepatocyte monolayers

Effects of potential modifiers on intracellular protein degradation have been measured in hepatocyte monolayers two days after the cells were isolated and plated. Modifiers were added after cells had been labelled with [3H]leucine and generally at the beginning of the degradation period. Protein degradation was inhibited by insulin, epidermal growth factor and serum as well as the protein synthesis inhibitors, leupeptin and weak bases. Degradation was stimulated by cyclic AMP, glucagon, beta-agonists, glucocorticoids and nutritional stepdown. The results from addition and competition experiments are consistent with all effectors acting on lysosomal proteolysis but differing in whether they alter amounts of proteinases, conditions favourable for proteinase function, or degree of autophagocytosis.