Glycosaminoglycan synthesis by cultured skin fibroblasts from a patient with Lowe's syndrome.
Glycosaminoglycan metabolism in cultured skin fibroblasts from a patient with Lowe's syndrome (oculocerebrorenal syndrome) was compared with that in normal fibroblasts. Cells were incubated with [3H]glucosamine and 35SO42-, and then the labeled glycosaminoglycans in the medium, trypsinate, and cell membrane fractions were analyzed by means of enzymatic and chemical degradations and by electrophoresis. Glycosaminoglycans, mostly chondroitin sulfates and dermatan sulfate, were markedly undersulfated in Lowe's syndrome. Undersulfation was most pronounced in the cell membrane fraction of cells which had been incubated at 0.03 mM sulfate concentration. Even at 0.52 mM or a higher sulfate concentration, undersulfation of chondroitin sulfates in the cell membrane fractions was significant. The undersulfation was the result of depressed sulfation rather than that of increased desulfation, as demonstrated by pulse-chase experiments using 35SO42-. Hyaluronate synthesis was not significantly impaired in the Lowe's syndrome fibroblasts. It was inferred, based on the results of the present study and those previously reported that the undersulfation of glycosaminoglycans is a consequence of a lower level of active sulfate (adenosine 3'-phosphate 5'-phosphosulfate) in the Lowe's syndrome fibroblasts, caused by an elevation of nucleotide pyrophosphatase activity degrading adenosine 3'-phosphate 5'-phosphosulfate.
D002455:Cell Division; D002478:Cells, Cultured; D002675:Child, Preschool; D005347:Fibroblasts / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006801:Humans; D007223:Infant; D007700:Kinetics; D008297:Male; D009800:Oculocerebrorenal Syndrome / Q000378:metabolism*; D015499:Renal Tubular Transport, Inborn Errors / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014316:Tritium
D006025:Glycosaminoglycans; D013431:Sulfates; D013462:Sulfur Radioisotopes; D014316:Tritium; D005944:Glucosamine