Cell Type Dependent Inhibition of Transport of Cathepsin D in HepG2 Cells and Fibroblasts Exposed to Deoxy-manno-nojirimycin and Deoxynojirimycin
- 1 January 1985
- journal article
- research article
- Published by Walter de Gruyter GmbH in Biological Chemistry Hoppe-Seyler
- Vol. 366 (2), 1009-1016
- https://doi.org/10.1515/bchm3.1985.366.2.1009
Abstract
The synthesis, transport and processing of lysosomal enzymes was examined in human hepatoma HepG2 cells and in human fibroblasts exposed to the Golgi .alpha.-mannosidase I inhibitor 1-deoxy-manno-nojirimycin. In HepG2 cells cathepsin D, .beta.-hexosaminidase and arylsulfatase B synthesized in the presence of 5 mM 1-deoxy-manno-nojirimycin contained exclusively endo-.beta.-N-acetylglucosaminidase H-cleavable oligosaccharides, indicating that .alpha.-mannosidase I had been inhibited efficiently. The proteolytic processing of intracellularly retained cathepsin D was retarded and the fraction of secreted cathepsin D was increased two-fold. In fibroblasts neither segregation nor maturation of cathepsin D were affected by 1-deoxy-manno-nojirimycin in spite of the inhibition of oligosaccharide processing. In the presence of the glucosidase I inhibitor 1-deoxynojirimycin, the precursor of cathepsin D (larger by about 1 kDa than the secreted form) accumulated transiently in light membranes in HepG2 cells. Release from the site of accumulation was accompanied by a decrease in size by about 1 kDa. This change was attributed to the removal of glucose residues. In fibroblasts the transient accumulation of larger precursors in the presence of 1-deoxynojirimycin was more pronounced than in HepG2 cells. The differential effects of .alpha.-mannosidase I and glucosidase I inhibitors on the transport of cathepsin D in HepG2 cells and fibroblasts may indicate that different intermediates in the biosynthetic pathway of asparagine-linked oligosaccharides participate in the transport of lysosomal enzymes in the two cell types.This publication has 27 references indexed in Scilit:
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