DIFFERENTIAL RATE OF CHOLESTEROL EFFLUX FROM THE APICAL AND BASOLATERAL MEMBRANES OF MDCK CELLS

Epithelial cells contain two distinct membrane surfaces, the apical and basolateral plasma membranes, which have different lipid and protein compositions. In or- der to assess the effect of the compositional differences of the apical and basolateral membranes on their ability to un- dergo cholesterol efflux, MDCK cells were radiolabeled with ( 3 H)cholesterol and grown as a polarized monolayer on filter inserts, that separate the upper apical compart- ment from the lower basolateral compartment. The rate of cholesterol efflux from the basolateral membrane into me- dia containing HDL in the basolateral compartment was 6.3%/h 6 0.7, whereas HDL-mediated efflux from the api- cal membrane was approximately 3-fold slower (1.9%/h 6 0.3). In contrast, Fu5AH cells, which do not form distinct polarized membrane domains, had a similar rate of HDL- mediated cholesterol efflux into the apical and basolateral compartments. Similar to HDL, other cholesterol accep- tors, namely LDL, bovine serum albumin, and a lipid emul- sion, also showed a decreased rate of cholesterol efflux from the apical membrane surface versus the basolateral membrane. Compared to the basolateral membrane, the apical membrane was also found to be more resistant to cholesterol oxidase treatment, to bind less HDL, and to take up less cholesterol from the medium. In conclusion, cholesterol efflux occurred less readily from the apical membrane than from the basolateral membrane for all types of acceptors tested. These results suggest that differ- ences in the composition of the apical and basolateral mem- brane lead to a relative decrease in cholesterol desorption from the apical membrane and hence a reduced rate of cho- lesterol efflux.— Remaley, A. T., B. D. Farsi, A. C. Shirali, J. M. Hoeg, and H. B. Brewer, Jr. Differential rate of choles- terol efflux from the apical and basolateral membranes of MDCK cells. J. Lipid Res. 1998. 39: 1231-1238.