出版社：American Society for Biochemistry and Molecular Biology
摘要：The major pathway for the removal of cholesterol from the bodyis via secretion into the bile. Three members of the ATP bindingcassette (ABC) family, ABCG5 (G5), ABCG8 (G8), and ABCB4 (MDR2),are required for the efficient biliary export of sterols. Here,we examined the interdependence of these three ABC transportersfor biliary sterol secretion. Biliary lipid levels in mice expressingno MDR2 (Mdr2–/– mice) were compared with thoseof Mdr2–/– mice expressing 14 copies of a humanG5 (hG5) and hG8 transgene (Mdr2–/–;hG5G8Tg mice).Mdr2–/– mice had only trace amounts of biliary cholesteroland phospholipids. The Mdr2–/–;hG5G8Tg mice hadbiliary cholesterol levels as low as those of Mdr2–/–mice. Thus, MDR2 expression is required for G5G8-mediated biliarysterol secretion. To determine whether the reduction in fractionalabsorption of dietary sterols associated with G5G8 overexpressionis secondary to the associated increase in biliary cholesterol,we compared the fractional absorption of sterols in Mdr2–/–;hG5G8Tgand hG5G8Tg animals. Inactivation of MDR2 markedly attenuatedthe reduction in fractional sterol absorption associated withG5G8 overexpression.
These results are consistent with the notion that increasedbiliary cholesterol secretion contributes to the reduction infractional sterol absorption associated with G5G8 overexpression.Abbreviations: G5, ATP binding cassette transporter G5; G8, ATP binding cassette transporter G8; MDR2, ATP binding cassette transporter B4
Supplementary key words ATP binding cassette transporters G5 and G8 • ATP binding cassette transporter B4 • sitosterol • campesterol • cholesterol absorption • bile acid • fecal sterol
