Rossi Antonio, Cetta Giuseppe, Piazza Rocco, Bonaventure Jacky, Steinmann Beat, Supereti-Furga Andrea
Dipartimento di Biochimica Alessandro Castellani, Università di Pavia, Pavia, Italy.
Pediatr Pathol Mol Med. 2003 Jul-Aug;22(4):311-21. doi: 10.1080/pdp.22.4.311.321.
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.
硫酸盐 - 氯离子反向转运体基因——脊柱骨骺发育不良硫酸盐转运体（DTDST）发生突变，与一系列骨骼发育不良相关，包括隐性多发性骨骺发育不良、脊柱骨骺发育不良（DTD）、2型atelosteogenesis和1B型软骨发育不全（ACG1B）。DTDST功能对于蛋白聚糖（PG）硫酸化所需的细胞外硫酸盐摄取至关重要；临床表型的组织特异性表达可能是软骨细胞中PG合成率高以及随之而来的高硫酸盐需求的结果。我们研究了半胱氨酸及其衍生物对硫酸盐转运体发育不良患者成纤维细胞和软骨细胞培养物中PG硫酸化的作用。通过硫酸软骨素PG的HPLC二糖分析测定，将ACG1B成纤维细胞在含有不同浓度胱氨酸的培养基中孵育表明PG硫酸化有部分恢复；用N - 乙酰半胱氨酸孵育后也观察到类似结果。当在一名DTD患者的原代软骨细胞中测试这两种化合物时，观察到PG硫酸化有部分挽救，表明从硫醇产生细胞质硫酸盐的代谢途径在这种细胞类型中也有活性。
