Alterations in cholesterol metabolism in cultured fibroblasts from patients with Niemann-Pick disease type C

Summary

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 studiedin vitro on cell homogenates. Chase experiments with¹⁴C-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.