Abstract
The pharmacological agent U18666A (3-beta-[2-(diethylamino)ethoxy]androst-5-en-17-one inhibits the intracellular transport of low density lipoprotein (LDL)-derived cholesterol in Chinese hamster ovary (CHO) cells. LDL-derived cholesterol accumulates in the lysosomes of U18666A-treated cells causing delayed LDL-mediated regulation of cellular cholesterol metabolism and impaired movement of LDL-derived cholesterol to other cell membranes. As a result of impaired LDL-derived cholesterol transport, LDL-dependent growth of CHO cells is also inhibited by U18666A. By selecting for cell growth in the presence of U18666A, we have identified a CHO cell line, designated U18R, that is resistant to U18666A-inhibition of LDL-derived cholesterol trafficking. When compared to parental CHO cells, U18R cells are relatively resistant to U18666A inhibition of LDL-derived cholesterol transport as well as LDL-mediated regulation of cellular cholesterol metabolism. In cell fusion experiments, the U18666A resistance observed in U18R cells displays a dominant phenotype. Identification of the U18666A-resistant factor may provide important insights toward the understanding of intracellular LDL-derived cholesterol regulation and trafficking.
Highlights
Resistant to U18666A inhibition of LDL-derived cho- inhibits the activity or synthesis of a protein or lipid that lesterol transport as well as LDL-mediated regulation facilitates cholesterol movement
U18R cells are resistant cholesterol transport has been of particular interest because to U18666A inhibition of theintracellular movement and of cholesterol's dual role as a structural component of the efflux of LDL-derived cholesterol
A CHO cell line that is resistant to U18666A inhibition of LDL-derived cholesterol transport was developed by taking advantage of this finding
Summary
Resistant to U18666A inhibition of LDL-derived cho- inhibits the activity or synthesis of a protein or lipid that lesterol transport as well as LDL-mediated regulation facilitates cholesterol movement. The U18666A-resistant factor may provide important T o identifythe U18666A-inhibitablecellular component insights toward the understanding of intracellular that modulates LDL-derived cholesterol movement, we have LDL-derived cholesterol regulation and trafficking. The. The existence of specific lipid sorting and transportmech- U18666A-resistant cell line, designated U18R, is resistant to anisms hasbeen evoked to explain the dfferepnht ospholipid U18666A inhibition of LDL stimulation of cholesterol esterand sterol compositions of various cellular membranes (re- ification and LDL suppressionof 3-hydroxy-3-methylglutaryl viewed in Ref. 1).Determining the mechanismof intracellular (HMG)-CoA reductaseactivity. U18R cells are resistant cholesterol transport has been of particular interest because to U18666A inhibition of theintracellular movement and of cholesterol's dual role as a structural component of the efflux of LDL-derived cholesterol. The costs of publication of this article were ' The abbreviations used are: U18666A, 3-@-[2-(diethylamino)-
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
