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 s ynthesized cathepsin D as a precursor that was either processed intrac ellularly to smaller mature forms or secreted into the medium. The pat tern of mature enzyme forms was different in the 2 cell types. In addi tion, the relative amount of precursor secreted was much higher for he patoma cells. Monensin strongly enhanced the secretion and also impair ed 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 matur ation 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 c ells than in hepatocytes; (ii) in the 2 cell types, delivery to lysoso mes and processing of procathepsin D were differently sensitive to inc reases in the vacuolar pH. (C) 1995 Wiley-Liss, Inc.