Differential Effects of Membrane Cholesterol Content on the Transport Activity of Multidrug Resistance–Associated Protein 2 (ABCC2) and of the Bile Salt Export Pump (ABCB11)

2014 ◽  
Vol 85 (6) ◽  
pp. 909-920 ◽  
Author(s):  
Christelle Guyot ◽  
Lia Hofstetter ◽  
Bruno Stieger
Keyword(s):  
Multidrug Resistance ◽  
Bile Salt ◽  
Cholesterol Content ◽  
Membrane Cholesterol ◽  
Bile Salt Export Pump ◽  
Transport Activity ◽  
Differential Effects

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

Bile salt excretion in skate liver is mediated by a functional analog of Bsep/Spgp, the bile salt export pump

2000 ◽  
Vol 278 (1) ◽  
pp. G57-G63 ◽  
Author(s):  
Nazzareno Ballatori ◽  
James F. Rebbeor ◽  
Gregory C. Connolly ◽  
David J. Seward ◽  
Benjamin E. Lenth ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Bile Salt ◽  
Rat Liver ◽  
Bile Salts ◽  
Plasma Membranes ◽  
Functional Characterization ◽  
Salt Transport ◽  
Positive Staining ◽  
Transport Activity ◽  
Canalicular Membrane

Biliary secretion of bile salts in mammals is mediated in part by the liver-specific ATP-dependent canalicular membrane protein Bsep/Spgp, a member of the ATP-binding cassette superfamily. We examined whether a similar transport activity exists in the liver of the evolutionarily primitive marine fish Raja erinacea, the little skate, which synthesizes mainly sulfated bile alcohols rather than bile salts. Western blot analysis of skate liver plasma membranes using antiserum raised against rat liver Bsep/Spgp demonstrated a dominant protein band with an apparent molecular mass of 210 kDa, a size larger than that in rat liver canalicular membranes, ∼160 kDa. Immunofluorescent localization with anti-Bsep/Spgp in isolated, polarized skate hepatocyte clusters revealed positive staining of the bile canaliculi, consistent with its selective apical localization in mammalian liver. Functional characterization of putative ATP-dependent canalicular bile salt transport activity was assessed in skate liver plasma membrane vesicles, with [3H]taurocholate as the substrate. [3H]taurocholate uptake into the vesicles was mediated by ATP-dependent and -independent mechanisms. The ATP-dependent component was saturable, with a Michaelis-Menten constant ( K m) for taurocholate of 40 ± 7 μM and a K m for ATP of 0.6 ± 0.1 mM, and was competitively inhibited by scymnol sulfate (inhibition constant of 23 μM), the major bile salt in skate bile. ATP-dependent uptake of taurocholate into vesicles was inhibited by known substrates and inhibitors of Bsep/Spgp, including other bile salts and bile salt derivatives, but not by inhibitors of the multidrug resistance protein-1 or the canalicular multidrug resistance-associated protein, indicating a distinct transport mechanism. These findings provide functional and structural evidence for a Bsep/Spgp-like protein in the canalicular membrane of the skate liver. This transporter is expressed early in vertebrate evolution and transports both bile salts and bile alcohols.

scholarly journals Measurement of Transport Activities of 3β-Hydroxy-Δ5-bile Acids in Bile Salt Export Pump and Multidrug Resistance-Associated Proteins Using LC-MS/MS

2013 ◽  
Vol 61 (5) ◽  
pp. 559-566 ◽  
Author(s):  
Tsuyoshi Murai ◽  
Kana Oda ◽  
Terutake Toyo ◽  
Hiroshi Nittono ◽  
Hajime Takei ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Bile Salt ◽  
Bile Acids ◽  
Bile Salt Export Pump ◽  
Associated Proteins
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