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Altered intracellular processing and enhanced secretion of procathepsin D in a highly deviated rat hepatoma
Author(s) -
Isidoro Ciro,
Demoz Marina,
De Stefanis Daniela,
Mainferme Francis,
Wattiaux Robert,
Baccino Francesco M.
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910600109
Subject(s) - intracellular , secretion , cathepsin d , ammonium chloride , monensin , biology , cell culture , cathepsin , enzyme , biochemistry , microbiology and biotechnology , chemistry , genetics , organic chemistry
Both freshly‐isolated rat hepatocytes and Morris hepatoma 7777 cells synthesized cathepsin D as a precursor that was either processed intracellulary 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 intralyso‐somal 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. © 1995 Wiley‐Liss, Inc.