The effect of mannose 6-phosphate on the turnover of the proteoglycans in the extracellular matrix of human fibroblasts |
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Authors: | J H Brauker C F Roff J L Wang |
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Affiliation: | 1. SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa, Japan;2. National Institute of Informatics, 2-1-2 Hitotsubashi, Chiyoda-ku, Tokyo, Japan;3. The University of Edinburgh, Edinburgh, UK;4. The University of Tokyo, Japan |
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Abstract: | Human fibroblasts (SL66) were cultured in medium containing 35SO2-4 to label the glycosaminoglycans (GAGs). The cells were then detached from the culture dish to leave radioactively-labeled components of the extracellular matrix, hereafter termed 35S-labeled substrate-attached material. When unlabeled SL66 fibroblasts were plated onto this 35S-labeled substrate-attached material, the cells mediated two distinct events: (a) release of radioactivity from the substrate-attached material into the medium; (b) degradation of certain glycosaminoglycans into radioactive components of very low molecular weight including free radioactive sulfate. In the presence of mannose 6-phosphate, however, the degradation of the substrate-attached material by SL66 cells was partially inhibited. Analyses of this effect in terms of the dose-response curve, saccharide specificity, ammonium chloride sensitivity, and the requirement for cells suggest that both an intracellular compartment and the mannose 6-phosphate receptor that binds lysosomal enzymes at the cell surface may play important roles in the turnover and degradation of certain proteoglycans in substrate-attached material. |
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