Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9886462 | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2005 | 9 Pages |
Abstract
The bile salt export pump (BSEP) of hepatocyte secretes conjugated bile salts across the canalicular membrane in an ATP-dependent manner. The biliary bile salts of human differ from those of rat in containing a greater proportion of glycine conjugates and taurolithocholate 3-sulfate (TLC-S). In the present study, the transport properties of hBSEP and rBsep were investigated using membrane vesicles from HEK293 cells infected with recombinant adenoviruses containing hBSEP or rBsep cDNA. ATP-dependent uptake of radiolabeled glycine-, taurine-conjugated bile salts, and [3H]cholate was observed when hBSEP or rBsep was expressed. Comparison of initial uptake rates indicated that for both transporters, taurine-conjugated bile salts were transported more rapidly than glycine-conjugated bile salts, however, hBSEP transported glycine conjugates to an extent that was approximately 2-fold greater than rBsep. In addition, [3H]TLC-S was significantly transported by hBSEP, and hardly transported by rBsep. The mean Km value for the uptake of [3H]TLC-S by hBSEP was 9.5 ± 1.5 μM, a value similar to that for hMRP2 (8.2 ± 1.3 μM). In conclusion, both hBSEP and rBsep transport taurine-conjugated bile salts better than glycine-conjugated bile salts, but hBSEP transports glycine conjugates to a greater extent as compared to rBsep. TLC-S, which is present in human bile but not rodent bile, is more avidly transported by hBSEP compared with rBsep.
Keywords
BSEP/BsepglycoursodeoxycholateGUDCTuDCUrsodeoxycholateTaurochenodeoxycholatetcdCchenodeoxycholatecholateTaurodeoxycholatetauroursodeoxycholateTDCGCDCDJSGFPPFICHEK293UDCACDCAABC transporterMOILCAtaurocholateDubin-Johnson syndromeLithocholateBile saltgreen fluorescent proteinmultiplicity of infectionProgressive familial intrahepatic cholestasishuman embryonic kidney 293glycochenodeoxycholateGlycocholate
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Authors
Hisamitsu Hayashi, Tappei Takada, Hiroshi Suzuki, Reiko Onuki, Alan F. Hofmann, Yuichi Sugiyama,