scholarly journals Activity of the Bile Salt Export Pump (ABCB11) Is Critically Dependent on Canalicular Membrane Cholesterol Content

2009 ◽  
Vol 284 (15) ◽  
pp. 9947-9954 ◽  
Author(s):  
Coen C. Paulusma ◽  
D. Rudi de Waart ◽  
Cindy Kunne ◽  
Kam S. Mok ◽  
Ronald P. J. Oude Elferink
Keyword(s):  
Bile Salt ◽  
Cholesterol Content ◽  
Membrane Cholesterol ◽  
Bile Salt Export Pump ◽  
Canalicular Membrane

Trafficking of the bile salt export pump from the Golgi to the canalicular membrane is regulated by the p38 MAP kinase

2004 ◽  
Vol 126 (2) ◽  
pp. 541-553 ◽  
Author(s):  
Ralf Kubitz ◽  
Gerrit Sütfels ◽  
Thomas Kühlkamp ◽  
Ralf Kölling ◽  
Dieter Häussinger
Keyword(s):  
Bile Salt ◽  
Map Kinase ◽  
P38 Map Kinase ◽  
Bile Salt Export Pump ◽  
Canalicular Membrane

Estradiol-17β-D-glucuronide induces endocytic internalization of Bsep in rats

2003 ◽  
Vol 285 (2) ◽  
pp. G449-G459 ◽  
Author(s):  
Fernando A. Crocenzi ◽  
Aldo D. Mottino ◽  
Jingsong Cao ◽  
Luis M. Veggi ◽  
Enrique J. Sánchez Pozzi ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Confocal Microscopy ◽  
Bile Salt ◽  
Western Blotting ◽  
Bile Flow ◽  
Harmful Effect ◽  
Bile Salt Export Pump ◽  
Canalicular Membrane ◽  
Estradiol 17Β

Endocytic internalization of the multidrug resistance-associated protein 2 (Mrp2) was previously suggested to be involved in estradiol-17β-d-glucuronide (E217G)-induced cholestasis. Here we evaluated in the rat whether a similar phenomenon occurs with the bile salt export pump (Bsep) and the ability of DBcAMP to prevent it. E217G (15 μmol/kg iv) impaired bile salt (BS) output and induced Bsep internalization, as assessed by confocal microscopy and Western blotting. Neither cholestasis nor Bsep internalization occurred in TR- rats lacking Mrp2. DBcAMP (20 μmol/kg iv) partially prevented the decrease in bile flow and BS output and substantially prevented E217G-induced Bsep internalization. In hepatocyte couplets, E217G (50 μM) diminished canalicular accumulation of a fluorescent BS and decreased Bsep-associated fluorescence in the canalicular membrane; DBcAMP (10 μM) fully prevented both effects. In conclusion, our results suggest that changes in Bsep localization are involved in E217G-induced impairment of bile flow and BS transport and that DBcAMP prevents this effect by stimulating insertion of canalicular transporter-containing vesicles. Mrp2 is required for E217G to induce its harmful effect.

scholarly journals Intracellular Trafficking of Bile Salt Export Pump (ABCB11) in Polarized Hepatic Cells: Constitutive Cycling between the Canalicular Membrane and rab11-positive Endosomes

2004 ◽  
Vol 15 (7) ◽  
pp. 3485-3496 ◽  
Author(s):  
Yoshiyuki Wakabayashi ◽  
Jennifer Lippincott-Schwartz ◽  
Irwin M. Arias
Keyword(s):  
Bile Salt ◽  
Intracellular Trafficking ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Confocal Imaging ◽  
Bile Salt Export Pump ◽  
Microtubule Organizing Center ◽  
Globular Structure ◽  
Canalicular Membrane ◽  
Organizing Center

The bile salt export pump (BSEP, ABCB11) couples ATP hydrolysis with transport of bile acids into the bile canaliculus of hepatocytes. Its localization in the apical canalicular membrane is physiologically regulated by the demand to secrete biliary components. To gain insight into how such localization is regulated, we studied the intracellular trafficking of BSEP tagged with yellow fluorescent protein (YFP) in polarized WIF-B9 cells. Confocal imaging revealed that BSEP-YFP was localized at the canalicular membrane and in tubulo-vesicular structures either adjacent to the microtubule-organizing center or widely distributed in the cytoplasm. In the latter two locations, BSEP-YFP colocalized with rab11, an endosomal marker. Selective photobleaching experiments revealed that single BSEP-YFP molecules resided in canalicular membranes only transiently before exchanging with intracellular BSEP-YFP pools. Such exchange was inhibited by microtubule and actin inhibitors and was unaffected by brefeldin A, dibutyryl cyclic AMP, taurocholate, or PI 3-kinase inhibitors. Intracellular carriers enriched in BSEP-YFP elongated and dissociated as tubular elements from a globular structure adjacent to the microtubule-organizing center. They displayed oscillatory movement toward either canalicular or basolateral membranes, but only fused with the canalicular membrane. The pathway between canalicular and intracellular membranes that BSEP constitutively cycles within could serve to regulate apical pools of BSEP as well as other apical membrane transporters.

Loss of bile salt export pump (Bsep/Abcb11) aggravates lipopolysaccharide induced hepatic inflammation in mice

2019 ◽  
Author(s):  
J Remetic ◽  
V Mlitz ◽  
V Kunczer ◽  
H Scharnagl ◽  
T Stojakovic ◽  
...  
Keyword(s):  
Bile Salt ◽  
Bile Salt Export Pump ◽  
Hepatic Inflammation
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