Braz J Med Biol Res, January 2008, Volume 41(1) 26-33
Niemann-Pick type C1 protein influences the delivery of cholesterol to the SREBP:SCAP complex
Y.J. Guo1,2, W.H. Li1, R. Wu1, Q. Xie1, Z.H. Zhang2 and 
L.Q. Cui2
1Department of Cardiology, The First Hospital of Xiamen, Fujian Medical University, Xiamen, China
2Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, China
The proposed role of Niemann-Pick type C1 protein (NPC1) in the delivery of low-density lipoprotein (LDL) cholesterol to the sterol regulatory element binding protein (SREBP):SREBP cleavage activation protein (SCAP) complex in the endoplasmic reticulum has been largely based on indirect studies and remains contentious. The major aim of the present study was to assess whether NPC1 is involved in the delivery of LDL cholesterol to the SREBP:SCAP complex. A cell line stably expressing green fluorescence protein-SCAP was cultured in the presence of U18666A, which can induce a Niemann-Pick type C disease phenotype, in order to locate the SREBP:SCAP complex by fluorescence microscopy. Our major finding was that defective NPC1 caused a delay in the ability of LDL cholesterol to suppress SREBP processing. This was shown in a time-course experiment by the effect of LDL on green fluorescence protein-SCAP movement when cells were treated with pharmacological agents to induce a Niemann-Pick type C disease phenotype. We demonstrated directly by fluorescence microscopy that defective NPC1 causes a delay in LDL cholesterol delivery to the endoplasmic reticulum where SCAP senses cholesterol.
Key words: Niemann-Pick type C1 protein; Low-density lipoprotein cholesterol; Fluorescence microscopy; Sterol regulatory element binding protein complex; Cholesterol homeostasis
Retraction
Braz J Med Biol Res, May 2008, Volume 41(5) 437 (Retraction)
Abstract
Publication Dates
-
Publication in this collection
17 Dec 2007 -
Date of issue
Jan 2008
