title: Effect of dimethylsulfoxide on sphingomyelinase activity and cholesterol metabolism in Niemann-Pick type C fibroblasts.
abstract: 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%, 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% DMSO (59.4 +/- 9.1 and 77.0 +/- 9.1 nmol h-1 mg protein-1, controls without and with 2% DMSO, respectively: 47.7 +/- 5.2 and 55.8 +/- 4.1 nmol h-1 mg protein-1. NPC without and with 2% 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% DMSO, 2% DMSO and 4% 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.
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul, RS, Brasil.
authors.forename: F B
authors.initials: FB
authors.lastname: Scalco
authors.forename: R
authors.initials: R
authors.lastname: Giugliani
authors.forename: P
authors.initials: P
authors.lastname: Tobo
authors.forename: J C
authors.initials: JC
authors.lastname: Coelho
mesh_terms: D000704:Analysis of Variance; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology* / Q000627:therapeutic use; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D009542:Niemann-Pick Diseases / Q000188:drug therapy / Q000201:enzymology*; D012997:Solvents / Q000494:pharmacology* / Q000627:therapeutic use; D013108:Sphingomyelin Phosphodiesterase / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D012997:Solvents; D002784:Cholesterol; D013108:Sphingomyelin Phosphodiesterase; D004121:Dimethyl Sulfoxide