Hepatic canalicular membrane transport of bile salt in C57L/J and AKR/J mice: implications for cholesterol gallstone formation.
Hepatic canalicular membrane transport of bile salt in C57L/J and AKR/J mice: implications for cholesterol gallstone formation.
复制标题
C57L/J 和 AKR/J 小鼠中胆汁盐的肝小管膜转运：对胆固醇胆结石形成的影响。
DOI：
10.1007/s00232-003-0620-4
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Green,RM
中科院分区：
文献类型：
--
作者：
Hoda,F;Green,RM
C57L/J (gallstone-susceptible) and AKR/J (gallstone-resistant) mice have been utilized for quantitative trait loci (QTL) analysis to identify theLith 1locus for cholelithiasis.Abcb11encodes for the liver canalicular membrane bile salt export pump (BSEP), which maps to this QTL and is a candidate gene forLith 1. We investigated the transmembrane transport of taurocholate in canalicular liver membrane vesicles isolated from these murine strains. Canalicular liver plasma membranes (cLPM) and RNA were isolated from C57L/J and AKR/J mice livers, and were utilized for Northern and Western blot analysis and functional3H-taurocholate uptake studies. ATP-dependent3H-taurocholate uptake was significantly higher in AKR/J, compared to C57L/J mice.Vmaxwas 127vs.42 pmol TC/mg/s in the murine strains, respectively, whileKmwas unchanged. In contrast, gene and protein expression of hepaticAbcb11was increased three-fold in C57L/J, compared to AKR/J mice. Thus,Abcb11bile salt transport activity per unit protein was reduced nine-fold in the C57L/J, compared to AKR/J mice. In contrast, canalicular membrane cholesterol:phospholipid content was also significantly higher in the C57L/J mice. We conclude that gallstone-susceptible C57L/J mice demonstrate increased gene and canalicular membrane expression ofAbcb11, however, taurocholate transport is functionally diminished. The latter may be due to the increased cholesterol membrane content of the cLPM in C57L/J mice. These findings may be important for the pathogenesis of gallstone formation.
