Cholesterol and plant sterol efflux from cultured intestinal epithelial cells is mediated by ATP-binding cassette transporters.
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.
Tachibana
Shizuko
S
Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, University of Tokyo, Tokyo, Japan.
Hirano
Maki
M
Hirata
Takashi
T
Matsuo
Michinori
M
Ikeda
Ikuo
I
Ueda
Kazumitsu
K
Sato
Ryuichiro
R
D064286:ATP Binding Cassette Transporter 1; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D001692:Biological Transport; D018938:Caco-2 Cells; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000819:agonists; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000166:cytology; D008074:Lipoproteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010840:Phytosterols / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists
C577836:ABCA1 protein, human; C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D064286:ATP Binding Cassette Transporter 1; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D004268:DNA-Binding Proteins; D008074:Lipoproteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010840:Phytosterols; D018160:Receptors, Cytoplasmic and Nuclear; D002784:Cholesterol