title: Overexpression of MDR1 in an intestinal cell line results in increased cholesterol uptake from micelles.
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 [(3)H]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.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. stensnlb@im.wustl.edu
authors.forename: T G
authors.initials: TG
authors.lastname: Tessner
authors.forename: W F
authors.initials: WF
authors.lastname: Stenson
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D015870:Gene Expression; D019450:Genes, MDR; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008823:Micelles; D051381:Rats; D014162:Transfection; D014700:Verapamil / Q000494:pharmacology; D014747:Vinblastine / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000906:Antibodies; D008823:Micelles; D014747:Vinblastine; D002784:Cholesterol; D014700:Verapamil