Résumé
Niemann-Pick type C (NPC) fibroblasts present a large concentration of cholesterol in their cytoplasm due to a still unidentified deficiency in cholesterol metabolism. The influence of dimethylsulfoxide (DMSO) on the amount of intracellular cholesterol was measured in 8 cultures of normal fibroblasts and in 7 fibroblast cultures from NPC patients. DMSO was added to the fibroblast cultures at three different concentrations (1, 2 and 4 percent, v/v) and the cultures were incubated for 24 h. Sphingomyelinase activity was significantly increased in both groups of cells only when incubated with 2 percent DMSO (59.4 9.1 and 77.0 9.1 nmol h-1 mg protein-1, controls without and with 2 percent DMSO, respectively; 47.7 5.2 and 55.8 4.1 nmol h-1 mg protein-1, NPC without and with 2 percent DMSO, respectively). However, none of the DMSO concentrations used altered the amount of cholesterol in the cytoplasm of NPC cells (0.704 0.049, 0.659 0.041, 0.688 0.063 and 0.733 0.088 mg/mg protein, without DMSO, 1 percent DMSO, 2 percent DMSO and 4 percent DMSO, respectively). This finding suggests that sphingomyelinase deficiency is a secondary defect in NPC and shows that DMSO failed to remove the stored cholesterol. These data do not support the use of DMSO in the treatment of NPC patients