475 Bile acid transport activity and intracellular distribution of PFIC2 mutants in MDCKII cells coexpressing NTCP and BSEP

Hepatology ◽  
2003 ◽  
Vol 38 ◽  
pp. 389-389 ◽  
Author(s):  
T KAGAWA ◽  
K MOCHIZUKI ◽  
M HARRIS ◽  
N WATANABE ◽  
T MINE ◽  
...  
Keyword(s):  
Bile Acid ◽  
Intracellular Distribution ◽  
Acid Transport ◽  
Transport Activity ◽  
Bile Acid Transport ◽  
Mdckii Cells

Sorting of rat liver and ileal sodium-dependent bile acid transporters in polarized epithelial cells

1998 ◽  
Vol 275 (5) ◽  
pp. G1045-G1055 ◽  
Author(s):  
An-Qiang Sun ◽  
Meenakshisundaram Ananthanarayanan ◽  
Carol J. Soroka ◽  
Sundararajah Thevananther ◽  
Benjamin L. Shneider ◽  
...  
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Mdck Cells ◽  
Cytoplasmic Tail ◽  
Apical Surface ◽  
Acid Transport ◽  
Transport Activity ◽  
Wild Type ◽  
Bile Acid Transport ◽  
Apical Domain

The rat ileal apical Na+-dependent bile acid transporter (ASBT) and the liver Na+-taurocholate cotransporting polypeptide (Ntcp) are members of a new family of anion transporters. These transport proteins share limited sequence homology and almost identical predicted secondary structures but are localized to the apical surface of ileal enterocytes and the sinusoidal surface of hepatocytes, respectively. Stably transfected Madin-Darby canine kidney (MDCK) cells appropriately localized wild-type ASBT and Ntcp apically and basolaterally as assessed by functional activity and immunocytochemical localization studies. Truncated and chimeric transporters were used to determine the functional importance of the cytoplasmic tail in bile acid transport activity and membrane localization. Two cDNAs were created encoding a truncated transporter in which the 56-amino-acid COOH-terminal tail of Ntcp was removed or substituted with an eight-amino-acid epitope FLAG. For both mutants there was some loss of fidelity in basolateral sorting in that ∼75% of each protein was delivered to the basolateral surface compared with ∼90% of the wild-type Ntcp protein. In contrast, deletion of the cytoplasmic tail of ASBT led to complete loss of transport activity and sorting to the apical membrane. An Ntcp chimera in which the 56-amino-acid COOH-terminal tail of Ntcp was replaced with the 40-amino-acid cytoplasmic tail of ASBT was largely redirected (82.4 ± 3.9%) to the apical domain of stably transfected MDCK cells, based on polarity of bile acid transport activity and localization by confocal immunofluorescence microscopy. These results indicate that a predominant signal for sorting of the Ntcp protein to the basolateral domain is located in a region outside of the cytoplasmic tail. These studies have further shown that a novel apical sorting signal is localized to the cytoplasmic tail of ASBT and that it is transferable and capable of redirecting a protein normally sorted to the basolateral surface to the apical domain of MDCK cells.

scholarly journals The solute carrier family 10 (SLC10): Beyond bile acid transport

2013 ◽  
Vol 34 (2-3) ◽  
pp. 252-269 ◽  
Author(s):  
Tatiana Claro da Silva ◽  
James E. Polli ◽  
Peter W. Swaan
Keyword(s):  
Bile Acid ◽  
Solute Carrier Family ◽  
Acid Transport ◽  
Bile Acid Transport ◽  
Solute Carrier

Abnormal hepatic sinusoidal bile acid transport: New insights into the pathogenesis of cholestasis?

2001 ◽  
Vol 120 (1) ◽  
pp. 321-322 ◽  
Author(s):  
Michael Trauner ◽  
Peter Fickert ◽  
Gernot Zollner
Keyword(s):  
Bile Acid ◽  
Acid Transport ◽  
Bile Acid Transport

Bile acid transport by basal membrane vesicles of human term placental trophoblast

1990 ◽  
Vol 99 (5) ◽  
pp. 1431-1438 ◽  
Author(s):  
Jose J.G. Marin ◽  
Maria A. Serrano ◽  
Mohamad Y. El-Mir ◽  
Nelida Eleno ◽  
C.A.Richard Boyd
Keyword(s):  
Bile Acid ◽  
Membrane Vesicles ◽  
Basal Membrane ◽  
Acid Transport ◽  
Bile Acid Transport

Liver disease with altered bile acid transport in Niemann-Pick C mice on a high-fat, 1% cholesterol diet

2005 ◽  
Vol 289 (2) ◽  
pp. G300-G307 ◽  
Author(s):  
Robert P. Erickson ◽  
Achyut Bhattacharyya ◽  
Robert J. Hunter ◽  
Randall A. Heidenreich ◽  
Nathan J. Cherrington
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
High Fat Diet ◽  
Density Lipoprotein ◽  
Cholestatic Hepatitis ◽  
Diffuse Fibrosis ◽  
Acid Transport ◽  
High Fat ◽  
Bile Acid Transport ◽  
Niemann Pick

Cholestatic hepatitis is frequently found in Niemann-Pick C (NPC) disease. We studied the influence of diet and the low density lipoprotein receptor (LDLR, Ldlr in mice, known to be the source of most of the stored cholesterol) on liver disease in the mouse model of NPC. Npc1−/− mice of both sexes, with or without the Ldlr knockout, were fed a 18% fat, 1% cholesterol (“high-fat”) diet and were evaluated by chemical and histological methods. Bile acid transporters [multidrug resistance protein (Mrps) 1–5; Ntcp, Bsep, and OatP1, 2, and 4] were quantitated by real-time RT-PCR. Many mice died prematurely (within 6 wk) with hepatomegaly. Histopathology showed an increase in macrophage and hepatocyte lipids independent of Ldlr genotype. Non-zone-dependent diffuse fibrosis was found in the surviving mice. Serum alanine aminotransferase was elevated in Npc1−/− mice on the regular diet and frequently became markedly elevated with the high-fat diet. Serum cholesterol was increased in the controls but not the Npc1−/− mice on the high-fat diet; it was massively increased in the Ldlr−/− mice. Esterified cholesterol was greatly increased by the high-fat diet, independent of Ldlr genotype. γ-Glutamyltransferase was also elevated in Npc1−/− mice, more so on the high-fat diet. Mrps 1–5 were elevated in Npc1−/− liver and became more elevated with the high-fat diet; Ntcp, Bsep, and OatP2 were elevated in Npc1−/− liver and were suppressed by the high-fat diet. In conclusion, Npc1−/− mice on a high-fat diet provide an animal model of NPC cholestatic hepatitis and indicate a role for altered bile acid transport in its pathogenesis.

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