The effect of mannose 6-phosphate on the turnover of the proteoglycans in the extracellular matrix of human fibroblasts.
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.
D000643:Ammonium Chloride / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts; D006025:Glycosaminoglycans / Q000378:metabolism; D006600:Hexosephosphates / Q000494:pharmacology*; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology; D008360:Mannosephosphates / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism*
D006025:Glycosaminoglycans; D006600:Hexosephosphates; D008360:Mannosephosphates; D011509:Proteoglycans; D000643:Ammonium Chloride; C027693:mannose-6-phosphate; D006867:Hydrolases