Altered intracellular processing and enhanced secretion of procathepsin D in a highly deviated rat hepatoma.
Both freshly-isolated rat hepatocytes and Morris hepatoma 7777 cells synthesized cathepsin D as a precursor that was either processed intracellular to smaller mature forms or secreted into the medium. The pattern of mature enzyme forms was different in the 2 cell types. In addition, the relative amount of precursor secreted was much higher for hepatoma cells. Monensin strongly enhanced the secretion and also impaired the intracellular transport-linked maturation of procathepsin D in hepatocytes, while it markedly inhibited intracellular maturation and only slightly increased secretion of the pro-enzyme in hepatoma cells. Ammonium chloride influenced the intralysosomal segregation and maturation of procathepsin D in hepatocytes but not in hepatoma cells. Our observations indicate that (i) the lysosomal segregation of cathepsin D was less efficient and its fractional secretion higher in hepatoma cells than in hepatocytes; (ii) in the 2 cell types, delivery to lysosomes and processing of procathepsin D were differently sensitive to increases in the vacuolar pH.
Isidoro
C
C
Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Italy.
Demoz
M
M
De Stefanis
D
D
Mainferme
F
F
Wattiaux
R
R
Baccino
F M
FM
D000818:Animals; D002402:Cathepsin D / Q000096:biosynthesis / Q000378:metabolism*; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D014407:Tumor Cells, Cultured; D014617:Vacuoles / Q000378:metabolism
D004792:Enzyme Precursors; C058345:procathepsin D; D002402:Cathepsin D