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A more recent version of this article appeared on August 1, 2005

Papers In Press, published online ahead of print June 1, 2005
J. Lipid Res., doi:10.1194/jlr.M500130-JLR200
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Submitted on April 4, 2005
Revised on May 9, 2005
Accepted on May 18, 2005

Niemann-Pick C1 (NPC1) expression is not regulated by the amount of cholesterol flowing through cells in the mouse

William S. Garver, Chonglun Xie, Joyce J. Repa, Stephen D. Turley, and John M. Dietschy

Pediatrics Dept., The University of Arizona, Arizona Health Science Center, Tucson, AZ 85724

Corresponding Author: wgarver{at}peds.arizona.edu

The Niemann-Pick C1 (NPC1) protein functions to regulate the transport of cholesterol from late endosomes/lysosomes to other cellular compartments after lipoprotein uptake through the coated-pit pathway. The present study examines the relative expression of NPC1 mRNA and NPC1 protein in different tissues of the mouse in relation to uptake of total cholesterol carried in chylomicron remnants (CMr-TC), low density lipoproteins (LDL-TC), cholesteryl ester carried in high density lipoproteins (HDL-CE) and cholesterol synthesis. Results from this study demonstrate that the highest relative expression of NPC1 is in the liver, which is also the tissue with the highest uptake of CMr-TC, LDL-TC, HDL-CE and cholesterol synthesis. However, there was no similar relation in the remaining tissues. To examine the relative expression of NPC1 in relation to the amount of cholesterol that flowed through the coated-pit pathway, mice were fed a diet supplemented with increasing amounts of cholesterol or cholestyramine. The results from this study demonstrated that there was no relation between the relative expression of NPC1 and the amount of cholesterol that flowed through the coated-pit pathway. We conclude that the relative expression of NPC1 is not regulated by the flow of cholesterol through cells in the mouse, and is therefore constitutive.


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