抄録
Biliary lipids consist of a mixture of bile salts, phospholipids and cholesterol. Monomers and simple micelles of bile salts have potent detergent properties and deleterious effects on cell membranes, which coexist with mixed micelles and vesicles of biliary lipid in a dynamic equilibrium in bile. In the presence of bile salts monomers, ABCB4, belonging to the ATP–binding cassette (ABC) transporter family, secretes the biliary phospholipids, preferentially phosphatidylcholine (PC). The formation of bile salts/PC mixed micelles protects hepatocytes from bile salts cytotoxicity by decreasing the cell association of bile salt molecules. On the other hand, cholesterol inhibits the interaction between bile salts and PC, and hence attenuates the cytoprotective effects of PC against bile salts. The ABCB4– mediated PC efflux is significantly increased by taurohyodeoxycholate, which has high mixed micelle formation ability with PC. These findings will help to develop new therapeutic agents for cholestatic liver diseases.
