Scavenger receptor class B type I reduces cholesterol absorption in cultured enterocyte CaCo-2 cells

Lei Cai, Erik R. M. Eckhardt, Wei Shi, Zhenze Zhao, Munira Nasser, Willem J. S. de Villiers, and Deneys R. van der Westhuyzen

Internal Medicine, University of Kentucky, Lexington, KY 40536-0298

Corresponding Author: dvwest1{at}uky.edu

Scavenger Receptor class B type I (SR-BI) mediates selective uptake of cholesteryl esters from HDL as well as efflux of cellular free cholesterol to HDL. It is unclear whether the receptor is involved in intestinal cholesterol absorption. We addressed this issue by studying [3H] cholesterol flux in differentiated CaCo-2 cells incubated at their apical side with mixed taurocholate/phosphatidylcholine/cholesterol micelles. Biotinylation and HDL binding experiments showed predominant apical expression of endogenous and over-expressed SR-BI. Mixed micellar cholesterol saturation affected magnitude and direction of cholesterol flux with significant net uptake only from supersaturated micelles and net efflux in case of unsaturated micelles. Incubation with micelles that depleted cellular cholesterol resulted in a decrease of SR-BI protein whereas incubation with cholesterol-loading micelles resulted in a significant increase of SR-BI protein. Apical cholesterol uptake by CaCo-2 cells was increased in presence of a SR-BI blocking antibody and by partial inhibition of SR-BI expression with small inhibitory RNA. Adenovirus-mediated over-expression of apical SR-BI did not affect cholesterol uptake, but stimulated apical cholesterol efflux, even to super-saturated mixed micelles. Partial inhibition of SR-BI with small inhibitory RNA reduced apical cholesterol efflux. Our data argue against a direct role for SR-BI in micellar cholesterol uptake. However, SR-BI might be involved in cholesterol absorption by facilitating cholesterol efflux to micelles.

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