Metabolism of sphingomyelin in cultured skin fibroblasts from patients with different types of Niemann-Pick disease.

Abstract

The metabolism of [choline-methyl-14C] sphingomyelin in cultured skin fibroblasts from patients with different types of Niemann-Pick disease was measured 1 and 3 days after uptake from the media. The cell lines obtained from type A disease had more than 95° unhydrolyzed sphingomyelin in situ on day 3 while two cell lines obtained from type B had 36.3° and 43.3° unhydrolyzed sphingomyelin on day 3. The cell line derived from one patient with the transitory type disease had 48.1% unhydrolyzed sphingomyelin on day 3, and there was no significant difference in the sphingomyelinase activity measured in vitro or in degradation of sphingomyelin in situ between the type B and transitory type disease. In three cell lines from patients with type C disease, there was 18.5° , 29.6% and 31.1% unhydrolyzed sphingomyelin on day 3, which indicates that this type has a decreased ability to metabolize sphingomyelin. Cell from type E disease metabolized sphingomyelin normally.Niemann-Pick disease ; [choline-methyl-14C] sphingomyelin ; metabolism ; cultured skin fibroblasts Niemann-Pick disease refers to a group of genetic diseases in which sphingomyelin is stored in certain tissues. The disease is classified into several clinical types (Brady 1983;Elleder and Jirasek 1983). In types A and B of this disease, the specific activity of sphingomyelinase is markedly reduced in cultured skin fibroblasts, whereas in types C. D and E it is characteristically near normal.The in vitro measurement of lysosomal enzyme activities is not a good predictor of the clinical course (Porter et al. 1971;Kudoh and Wenger 1982). Thus, the study of the uptake and metabolism of radiolabeled substrates by cultured skin fibroblasts has been suggested to more closely reflect the in vivo metabolism of such substrates (Kudoh et al. 1981;Kudoh and Wenger 1982).