Article: article from journal or magazin.
Case report (case report): feedback on an observation with a short commentary.
In vitro proteoglycan sulfation derived from sulfhydryl compounds in sulfate transporter chondrodysplasias.
Pediatric Pathology & Molecular Medicine
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Mutations in a sulfate-chloride antiporter gene, the diastrophic dysplasia sulfate transporter (DTDST), have been associated with a family of skeletal dysplasias including recessive multiple epiphyseal dysplasia, diastrophic dysplasia (DTD), atelosteogenesis type 2, and achondrogenesis type 1B (ACG1B). DTDST function is crucial for uptake of extracellular sulfate required for proteoglycan (PG) sulfation; the tissue-specific expression of the clinical phenotype may be the consequence of the high rate of PG synthesis in chondrocytes and the ensuing high sulfate requirement. We have studied the contribution of cysteine and its derivatives to PG sulfation in fibroblast and chondrocyte cultures from sulfate transporter dysplasia patients. Incubation of ACG1B fibroblasts in medium containing different concentrations of cystine indicated partial recovery of PG sulfation as measured by HPLC disaccharide analysis of chondroitin sulfate PGs; similar results were observed after incubation with N-acetylcysteine. When both compounds were tested in primary chondrocytes from a DTD patient, partial rescue of PG sulfation was observed, suggesting that the metabolic pathways producing cytoplasmic sulfate from thiols are also active in this cell type.
Acetylcysteine/metabolism, Achondroplasia/genetics, Achondroplasia/metabolism, Anion Transport Proteins, Base Sequence, Camurati-Engelmann Syndrome/genetics, Camurati-Engelmann Syndrome/metabolism, Carrier Proteins/genetics, Carrier Proteins/metabolism, Cartilage, Articular/pathology, Cells, Cultured, Chondrocytes/metabolism, Chondrocytes/pathology, Chondroitin Sulfates/analysis, Chondroitin Sulfates/metabolism, Chromatography, High Pressure Liquid, Cystamine/metabolism, Cysteine/metabolism, Disaccharides/analysis, Disaccharides/chemistry, Fetus, Fibroblasts/metabolism, Fibroblasts/pathology, Humans, Membrane Transport Proteins, Proteoglycans/metabolism, Sequence Deletion, Skin/pathology, Sulfates/metabolism, Sulfates/pharmacokinetics, Sulfhydryl Compounds/metabolism
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