The sterol transporting heterodimer ABCG5/ABCG8 requires bile salts to mediate cholesterol efflux.
The ATP binding cassette transporters ABCG5 and ABCG8 are indispensable for hepatobiliary cholesterol transport. In this study, we investigated the specificity of the heterodimer for cholesterol acceptors. Dog gallbladder epithelial cells were mono- or double-transfected with lentiviral mouse Abcg5 and Abcg8 vectors. Double-transfected cells showed increased efflux to different bile salt (BS) species, while mono-transfected cells did not show enhanced efflux. The efflux was initiated at micellar concentrations and addition of phosphatidylcholine increased efflux. Cholesterol secretion was highly BS dependent, whereas other cholesterol acceptors such as ApoAI, HDL or methyl-beta-cyclodextrin did not elicit Abcg5/g8 dependent cholesterol secretion.
Vrins
Carlos
C
Academic Medical Center, Department of Medical Biochemistry, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Vink
Edwin
E
Vandenberghe
Kristin E
KE
Frijters
Raoul
R
Seppen
Jurgen
J
Groen
Albert K
AK
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D003505:Cyclodextrins / Q000494:pharmacology; D019281:Dimerization; D004285:Dogs; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D051379:Mice