Alterations in cholesterol metabolism in cultured fibroblasts from patients with Niemann-Pick disease type C.
Cholesterol synthesis, esterification and efflux were investigated in cultured fibroblasts from patients with Niemann-Pick disease type C. Sterol synthesis from sodium acetate was markedly increased in the two Niemann-Pick disease type C strains as compared to controls, either in the presence or absence of exogenous cholesterol supply by low-density lipoproteins. By contrast, cholesterol esterification was about 2-3-fold reduced when measured by oleic acid incorporation into cholesteryl esters and 10-15-fold reduced when measured with labelled free cholesterol as precursor, although acylcoenzyme-A:cholesterol acyltransferase activity was normal when studied in vitro on cell homogenates. Chase experiments with 14C-cholesterol demonstrated that the rate of cholesterol efflux was decreased by about 3-4-fold in fibroblasts from patients with Niemann-Pick disease type C. These results provide further evidence for alterations of sterol metabolism in Niemann-Pick disease type C and support the hypothesis of a trapping of exogenous cholesterol, which cannot enter the regulatory intracellular pools.
D001345:Autoradiography; D002478:Cells, Cultured; D002675:Child, Preschool; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D004951:Esterification; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D009542:Niemann-Pick Diseases / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism
D009829:Oleic Acids; D019301:Oleic Acid; D002784:Cholesterol