Overexpression of MDR1 in an intestinal cell line results in increased cholesterol uptake from micelles

Teresa G. Tessner, William F. Stenson

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The multiple drug resistance protein, MDR1, is highly expressed on the apical surface of intestinal epithelial cells. The physiologic substrate of this protein remains unclear. Several studies using compounds known to act as MDR1 inhibitors have suggested that MDR1 may be involved in the transport of cholesterol from the plasma membrane to the endoplasmic reticulum where it is esterified. To examine the role of MDR1 in cholesterol uptake by intestinal cells, the rat intestinal epithelial cell line IEC-18, was stably transfected with human MDR1. MDR1-transfected cells exhibited increased expression of MDR1 protein, reduced accumulation of vinblastine and increased uptake of [3H]cholesterol from cholesterol/monolein/taurocholate micelles. These studies provide the first direct evidence that the level of MDR1 expression in intestinal cells can influence the amount of cholesterol taken up by those cells. This is also the first demonstration that a multiple drug resistance protein can function in the net uptake, rather than efflux, of a substrate. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)565-571
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume267
Issue number2
DOIs
StatePublished - Jan 19 2000

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