Synthesis and sulfation of glycosaminoglycans in fibroblasts from a patient with Lowe's syndrome

Glycosaminoglycans of cultured normal skin fibroblasts and fibroblasts of a patient with Lowe's syndrome were labelled for 72 h with either [14C]-glucosamine or with 35SO4. For each culture, the incorporation was measured in total glycosaminoglycans per culture and in the glycosaminoglycans isolated from the intracellular, pericellular and extracellular pools. The synthesis of the sulfated glycosaminoglycans in the three pools and the total 35SO4 incorporation in the glycosaminoglycans of the two types of cultures were strictly comparable. However, Lowe's intracellular glycosaminoglycans were less sulfated than the corresponding normal ones. Undersulfated glycosaminoglycans were present in the pericellular pool of Lowe's cells, while hypersulfated ones were present in their extracellular pool. Degradation of the different pools with chondroitinases indicated that hyposulfated chondroitin 4- and 6-sulfates are present on the cell surface of Lowe's cells, where an increased amount of normally sulfated heparan sulfate may be demonstrated. This abnormal distribution of pericellular glycosaminoglycans in Lowe's cells has been described already. However, the demonstration that the total incorporation of 35SO4 is normal in Lowe's cells does not support the possibility that this abnormal distribution is the consequence of excessive hydrolysis of the phosphosulfate bond of adenosine 3'-phosphate 5'-phosphosulfate.