Academic Journal

The mechanism of ABCG5/ABCG8 in biliary cholesterol secretion in mice1

التفاصيل البيبلوغرافية
العنوان: The mechanism of ABCG5/ABCG8 in biliary cholesterol secretion in mice1
المؤلفون: Astrid Kosters, Cindy Kunne, Norbert Looije, Shailendra B. Patel, Ronald P.J. Oude Elferink, Albert K. Groen
المصدر: Journal of Lipid Research, Vol 47, Iss 9, Pp 1959-1966 (2006)
بيانات النشر: Elsevier, 2006.
سنة النشر: 2006
المجموعة: LCC:Biochemistry
مصطلحات موضوعية: liver, canalicular membrane, bile salt infusion, diosgenin, Biochemistry, QD415-436
الوصف: The main player in biliary cholesterol secretion is the heterodimeric transporter complex, ABCG5/ABCG8, the function of which is necessary for the majority of sterols secreted into bile. It is not clear whether the primary step in this process is flopping of cholesterol from the inner to the outer leaflet of the canalicular membrane, with desorption by mixed micelles, or decreasing of the activation energy required for cholesterol desorption from the outer membrane leaflet. In this study, we investigated these mechanisms by infusing Abcg8+/+, Abcg8+/−, and Abcg8−/− mice with hydrophilic and hydrophobic bile salts. In Abcg8−/− mice, this failed to substantially stimulate biliary cholesterol secretion. Infusion of the hydrophobic bile salt taurodeoxycholate also resulted in cholestasis, which was induced in Abcg8−/− mice at a much lower infusion rate compared with Abc8−/− and Abcg8+/− mice, suggesting a reduced cholesterol content in the outer leaflet of the canalicular membrane. Indeed, isolation of canalicular membranes revealed a reduction of 45% in cholesterol content under these conditions in Abcg8−/− mice. Our data support the model that ABCG5/ABCG8 primarily play a role in flopping cholesterol (and sterols) from the inner leaflet to the outer leaflet of the canalicular membrane.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 0022-2275
Relation: http://www.sciencedirect.com/science/article/pii/S0022227520434625; https://doaj.org/toc/0022-2275
DOI: 10.1194/jlr.M500511-JLR200
URL الوصول: https://doaj.org/article/10281a93c41143c5947757e207305fe5
رقم الانضمام: edsdoj.10281a93c41143c5947757e207305fe5
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:00222275
DOI:10.1194/jlr.M500511-JLR200