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... C57L/J (gallstone-susceptible) and AKR/J (gallstone-resistant) mice have been utilized for quantitative trait loci (QTL) analysis to identify the Lith 1 locus for cholelithiasis. Abcb11 encodes for the liver canalicular membrane bile salt export pump (BSEP), which maps to this QTL and is a candidate gene for Lith 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 functional 3H-taurocholate uptake studies. ATP-dependent 3H-taurocholate uptake was significantly higher in AKR/J, compared to C57L/J mice. V max was 127 vs. 42 pmol TC/mg/s in the murine strains, respectively, while K m was unchanged. In contrast, gene and protein expression of hepatic Abcb11 was increased three-fold in C57L/J, compared to AKR/J mice. Thus, Abcb11 bile 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 of Abcb11, 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Hepatic Canalicular Membrane Transport of Bile Salt in C57L/J and AKR/J Mice: Implications for Cholesterol Gallstone Formation

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Publisher
Springer-Verlag
Copyright
Copyright © 2003 by Springer-Verlag New York Inc.
Subject
Philosophy
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-003-0620-4
Publisher site
See Article on Publisher Site

Abstract

C57L/J (gallstone-susceptible) and AKR/J (gallstone-resistant) mice have been utilized for quantitative trait loci (QTL) analysis to identify the Lith 1 locus for cholelithiasis. Abcb11 encodes for the liver canalicular membrane bile salt export pump (BSEP), which maps to this QTL and is a candidate gene for Lith 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 functional 3H-taurocholate uptake studies. ATP-dependent 3H-taurocholate uptake was significantly higher in AKR/J, compared to C57L/J mice. V max was 127 vs. 42 pmol TC/mg/s in the murine strains, respectively, while K m was unchanged. In contrast, gene and protein expression of hepatic Abcb11 was increased three-fold in C57L/J, compared to AKR/J mice. Thus, Abcb11 bile 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 of Abcb11, 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.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Jan 1, 2003

References

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