[Changes in the biosynthesis, esterification and efflux of cholesterol in fibroblasts in culture from patients with Niemann-Pick disease type C].
Cholesterol synthesis, esterification and efflux have been comparatively studied in control fibroblasts and in fibroblasts from patients with Niemann-Pick disease type C (NPC). Sterol synthesis was markedly increased in NPC cells as compared to controls, either in whole medium or in medium devoid of lipoproteins. 14C-oleic acid incorporation into cholesteryl-esters was 2 to 3 fold reduced in NPC cells, and esterification of 14C-exogenous cholesterol was dramatically (15-30 fold) decreased. ACAT activity, measured in vitro, was not significantly altered in NPC cells. Finally, cholesterol efflux appeared to be decreased in NPC fibroblasts as compared to controls. The hypothesis of a defect in exogenous cholesterol access to intracellular regulatory pools is proposed.
D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D004951:Esterification; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D009542:Niemann-Pick Diseases / Q000378:metabolism*; D009829:Oleic Acids / Q000378:metabolism
D002788:Cholesterol Esters; D009829:Oleic Acids; D002784:Cholesterol
Altérations de la biosynthèse, de l'estérification et de l'efflux du cholestérol dans les fibroblastes en culture de sujets atteints de maladie de Niemann-Pick type C.