Cholesterol Movement in Niemann-Pick Type C Cells and in Cells Treated with Amphiphiles *

摘要: Cholesterol accumulates to massive levels in cells from Niemann-Pick type C (NP-C) patients and treated with class 2 amphiphiles that mimic NP-C disease. This behavior has been attributed the failure of cholesterol released ingested low density lipoproteins exit lysosomes. However, we now show rate movement lysosomes plasma membranes is at least as great normal, was also found previously for amphiphile-treated cells. Furthermore, these filled membrane absence lipoproteins. In addition, showed size endoplasmic reticulum pool set point homeostatic sensor cell were approximately normal The pools both normal. build up not a physiological response overload. Rather, it appeared accumulation results an imbalance brisk flow among compartments. related experiments, did respond (e.g.trifluoperazine, imipramine, U18666A); agents may therefore act directly on NPC1 protein or its pathway. Finally, lysosomal substantially preferentially reduced by incubating oxysterols, 25-hydroxycholesterol 7-ketocholesterol; findings suggest new pharmacological approach treatment