title: Elevated activity and increased mannose-6-phosphate in the carbohydrate moiety of cathepsin D from human hepatoma.
abstract: A significant elevation of cathepsin D activity was observed in six human hepatoma tissues as compared to 12 normal human livers. In isoelectric focusing experiments, cathepsin D purified from normal liver exhibited three different forms, with isoelectric points of 5.6, 6.1, and 6.7, while cathepsin D purified from hepatoma contained another five to six more acidic forms in addition to the forms observed in normal liver cathepsin D. When the tumor enzyme was treated with endo-beta-N-acetylglucosaminidase H followed by isoelectric focusing, the acidic components disappeared and were converted to forms identical to those of the normal liver cathepsin D. Determination of the mannose-6-phosphate content showed that hepatoma cathepsin D contains twice as much mannose-6-phosphate as normal liver cathepsin D. Peptide mapping and amino acid analysis showed that the protein moiety of cathepsin D from hepatoma is almost identical with that from normal liver. These findings indicate that the appearance of acidic variants in hepatoma cathepsin D is mainly due to changes in the oligosaccharide chains of the enzyme, which are closely associated with the increase of mannose-6-phosphate in the tumor enzyme.
authors.affiliation: Biochemistry Laboratory, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Maguchi
authors.forename: N
authors.initials: N
authors.lastname: Taniguchi
authors.forename: A
authors.initials: A
authors.lastname: Makita
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D002402:Cathepsin D / Q000032:analysis* / Q000302:isolation & purification; D006600:Hexosephosphates / Q000032:analysis*; D006801:Humans; D006867:Hydrolases / Q000494:pharmacology; D007525:Isoelectric Focusing; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology*; D008360:Mannosephosphates / Q000032:analysis*; D010449:Peptide Mapping
chemical_list: D006600:Hexosephosphates; D008360:Mannosephosphates; C027693:mannose-6-phosphate; D006867:Hydrolases; D002402:Cathepsin D