Niemann-Pick C1 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; John M. Dietschy

doi:10.1194/jlr.M500130-JLR200

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

^*Department of Pediatrics, Arizona Health Sciences Center, University of Arizona, Tucson, AZ 85724
^†Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390
^§Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390

1To whom correspondence should be addressed. e-mail: wgarver{at}peds.arizona.edu

Abstract

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 the 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.

Footnotes

Published, JLR Papers in Press, June 1, 2005. DOI 10.1194/jlr.M500130-JLR200
- apoA-I, apolipoprotein A-I
- CMr-TC, total cholesterol carried in chylomicron remnants
- HDL-CE, cholesteryl ester carried in high density lipoproteins
- LDL-TC, total cholesterol carried in low density lipoproteins
- LDLR, low density lipoprotein receptor
- NPC1, Niemann-Pick C1
- NPC1L1, Niemann-Pick C1-Like 1
- SCAP, sterol regulatory element binding protein cleavage-activating protein
- SR-BI, scavenger receptor class B type 1