Cholesterol and Plant Sterol Efflux from Cultured Intestinal Epithelial Cells Is Mediated by ATP-Binding Cassette Transporters

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  • TACHIBANA Shizuko
    Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, University of Tokyo
  • HIRANO Maki
    Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, University of Tokyo
  • HIRATA Takashi
    Division of Applied Life Science, Graduate School of Agriculture, Kyoto University
  • MATSUO Michinori
    Division of Applied Life Science, Graduate School of Agriculture, Kyoto University
  • IKEDA Ikuo
    Department of Science of Food Function and Health, Graduate School of Agricultural Science, Tohoku University
  • UEDA Kazumitsu
    Division of Applied Life Science, Graduate School of Agriculture, Kyoto University
  • SATO Ryuichiro
    Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, University of Tokyo

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In this study we analyzed functions of ATP-binding cassette (ABC) transporters involved in sterol transport from Caco-2 cells. Treatment with a synthetic liver x receptor ligand elevated both mRNA and protein levels of ABCG5, G8, and ABCA1. The ligand stimulated cholesterol efflux, suggesting that ABC transporters are involved in it. To identify the acceptors of cholesterol, potential molecules such as apolipoprotein A-I, glycocholic acid, phosphatidylcholine, and bile acid micelles were added to the medium. Apo A-I, a known acceptor of cholesterol transported by ABCA1, elevated cholesterol efflux on the basal side, whereas the others raised cholesterol efflux on the apical side. Moreover, bile acid micelles preferentially augmented plant sterol efflux rather than cholesterol. Finally, in HEK293 cells stably expressing ABCG5/G8, bile acid micelle-mediated sterol efflux was significantly accelerated. These results indicate that ABCG5/G8, unlike ABCA1, together with bile acids should participate in sterol efflux on the apical surface of Caco-2 cells.

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