The thiol proteinase inhibitors, Z-Phe-PheCHN2 and Z-Phe-AlaCHN2, inhibit lysosomal protein degradation in isolated rat hepatocytes.
The effects on protein metabolism of Z-Phe-PheCHN2 and Z-Phe-AlaCHN2 were examined in isolated rat hepatocytes. The two thiol proteinase inhibitors caused a drastic reduction in the degradation of both endogenous and endocytosed (asialo-fetuin) protein. The inhibition was not additive to that of the lysosomotropic base methylamine, indicating that Z-Phe-PheCHN2 and Z-Phe-AlaCHN2 only affect lysosomal degradation. At high concentrations (0.1-1 mM) both inhibitors reduced protein synthesis strongly. This finding indicates non-specific/toxic effects, which may limit the usefulness of the inhibitors.
D000818:Animals; D001212:Asialoglycoproteins; D003978:Diazomethane / Q000031:analogs & derivatives* / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D060748:Fetuins; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D000509:alpha-Fetoproteins / Q000378:metabolism
D001212:Asialoglycoproteins; D060748:Fetuins; D011480:Protease Inhibitors; D011506:Proteins; D000509:alpha-Fetoproteins; C017029:asialofetuin; C024918:benzyloxycarbonylphenylalanylalanine diazomethyl ketone; D003978:Diazomethane; C031947:benzyloxycarbonylphenylalanylphenylalanine diazomethyl ketone; D004121:Dimethyl Sulfoxide