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- Title
Functional Characterization of ABCB4 Mutations Found in Low Phospholipid-Associated Cholelithiasis (LPAC).
- Authors
Tae Hee Kim; Hyo Jin Park; Ji Ha Choi
- Abstract
Multidrug resistance 3 (MDR3) is expressed on the canalicular membrane of the hepatocytes and plays an important role in protecting the liver from bile acids. Altered ABCB4 gene expression can lead to a rare hepatic disease, low phospholipid-associated cholelithiasis (LPAC). In this study, we characterized 3 ABCB4 mutations in LPAC patients using various in vitro assay systems. We first measured the ability of each mutant to transport paclitaxel and then the mechanisms by which these mutations might change MDR3 transport activity were determined using immunoblotting, cell surface protein biotinylation, and immunofluorescence. Through a membrane vesicular transport assay, we observed that the uptake of paclitaxel was significantly reduced in membrane vesicles expressing 2 ABCB4 mutations, F165I and S320F. Both mutants showed significantly decreased total and cell surface MDR3 expression. These data suggest two missense mutations of ABCB4 may alter function of MDR3 and ultimately can be determined as LPAC-causing mutations.
- Subjects
PHOSPHOLIPIDS; GALLSTONES; MULTIDRUG resistance-associated proteins; GENETIC mutation; GENE expression profiling; IMMUNOFLUORESCENCE
- Publication
Korean Journal of Physiology & Pharmacology, 2013, Vol 17, Issue 6, p525
- ISSN
1226-4512
- Publication type
Article
- DOI
10.4196/kjpp.2013.17.6.525