[Study of intralysosomal protein catabolism using lysosomotropic agents--proteolysis and protease inhibitors]

Abstract

Inhibition of intralysosomal catabolism of proteins was studied in rat liver cells using lysosomotropic drugs suramin (single administration at a dose of 250 mg/kg within 24 and 48 hrs) and chloroquine (at a dose of 30 mg/100 g within 0.5, 1, 3, 6 and 12 hrs after administration). Suramine inhibited pure preparations of cathepsin B and L, while chloroquine inhibited cathepsins B, L and H. The inhibitors were effective in vitro at lower concentrations as compared with these administered in vivo. Less distinct inhibitory effect was observed in the incubation mixture containing an extract of rat liver lysosomes. After administration of the inhibitors in vivo the activity of lysosomal proteinases was not inhibited in rat liver homogenates, which appears to occur due to complex formation between these lysosomotropic drugs and proteins.