scholarly journals Early Identification of Clinically Relevant Drug Interactions With the Human Bile Salt Export Pump (BSEP/ABCB11)

2013 ◽  
Vol 136 (2) ◽  
pp. 328-343 ◽  
Author(s):  
Jenny M. Pedersen ◽  
Pär Matsson ◽  
Christel A. S. Bergström ◽  
Janet Hoogstraate ◽  
Agneta Norén ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Bile Salt ◽  
Early Identification ◽  
Bile Salt Export Pump ◽  
Human Bile

Genetic Variations of the ABC Transporter Gene ABCB11 Encoding the Human Bile Salt Export Pump (BSEP) in a Japanese Population

2009 ◽  
Vol 24 (3) ◽  
pp. 277-281 ◽  
Author(s):  
Su-Ryang Kim ◽  
Yoshiro Saito ◽  
Masaya Itoda ◽  
Keiko Maekawa ◽  
Manabu Kawamoto ◽  
...  
Keyword(s):  
Bile Salt ◽  
Abc Transporter ◽  
Japanese Population ◽  
Genetic Variations ◽  
Transporter Gene ◽  
Bile Salt Export Pump ◽  
Human Bile

scholarly journals Glibenclamide, ATP and metformin increases the expression of human bile salt export pump ABCB11

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1497
Author(s):  
Nisha Vats ◽  
Ravi Chandra Dubey ◽  
Madhusudana Girija Sanal ◽  
Pankaj Taneja ◽  
Senthil Kumar Venugopal
Keyword(s):  
Cell Signaling ◽  
Bile Salt ◽  
Real Time ◽  
Real Time Pcr ◽  
Intrahepatic Cholestasis ◽  
Bile Salt Export Pump ◽  
Data Set ◽  
Human Bile ◽  
Immune Activity ◽  
Human Liver Cell

Background: Bile salt export pump (BSEP/ABCB11) is important in the maintenance of the enterohepatic circulation of bile acids and drugs. Drugs such as rifampicin and glibenclamide inhibit BSEP. Progressive familial intrahepatic cholestasis type-2, a lethal pediatric disease, some forms of intrahepatic cholestasis of pregnancy, and drug-induced cholestasis are associated with BSEP dysfunction.  Methods: We started with a bioinformatic approach to identify the relationship between ABCB11 and other proteins, microRNAs, and drugs. A microarray data set of the liver samples from ABCB11 knockout mice was analyzed using GEO2R. Differentially expressed gene pathway enrichment analysis was conducted using ClueGo. A protein-protein interaction network was constructed using STRING application in Cytoscape. Networks were analyzed using Cytoscape. CyTargetLinker was used to screen the transcription factors, microRNAs and drugs. Predicted drugs were validated on human liver cell line, HepG2. BSEP expression was quantified by real-time PCR and western blotting. Results: ABCB11 knockout in mice was associated with a predominant upregulation and downregulation of genes associated with cellular component movement and sterol metabolism, respectively. We further identified the hub genes in the network. Genes related to immune activity, cell signaling, and fatty acid metabolism were dysregulated.  We further identified drugs (glibenclamide and ATP) and a total of 14 microRNAs targeting the gene. Western blot and real-time PCR analysis confirmed the upregulation of BSEP on the treatment of HepG2 cells with glibenclamide, ATP, and metformin. Conclusions: The differential expression of cell signaling genes and those related to immune activity in ABCB11 KO animals may be secondary to cell injury. We have found glibenclamide, ATP, and metformin upregulates BSEP. The mechanisms involved and the clinical relevance of these findings need to be investigated.

P0358 FUNCTIONAL ANALYSIS OF THE TRANSCRIPTIONAL REGULATION OF THE HUMAN BILE SALT EXPORT PUMP GENE

2004 ◽  
Vol 39 (Supplement 1) ◽  
pp. S192-S193
Author(s):  
J. A. Byrne ◽  
S. S. Strautnieks ◽  
G. Mieli-Vergani ◽  
R. J. Thompson
Keyword(s):  
Functional Analysis ◽  
Transcriptional Regulation ◽  
Bile Salt ◽  
Bile Salt Export Pump ◽  
Human Bile

The mechanism of increased biliary lipid secretion in mice with genetic inactivation of bile salt export pump

2015 ◽  
Vol 308 (5) ◽  
pp. G450-G457 ◽  
Author(s):  
K. E. R. Gooijert ◽  
R. Havinga ◽  
H. Wolters ◽  
R. Wang ◽  
V. Ling ◽  
...  
Keyword(s):  
Protein Expression ◽  
Bile Salt ◽  
Biliary Secretion ◽  
Biliary Lipid ◽  
Bile Salt Export Pump ◽  
Human Bile ◽  
Lipid Secretion ◽  
Canalicular Transporters ◽  
Expression Potential ◽  
And Control

Human bile salt export pump ( BSEP) mutations underlie progressive familial intrahepatic cholestasis type 2 (PFIC2). In the PFIC2 animal model, Bsep−/−mice, biliary secretion of bile salts (BS) is decreased, but that of phospholipids (PL) and cholesterol (CH) is increased. Under physiological conditions, the biliary secretion of PL and CH is positively related (“coupled”) to that of BS. We aimed to elucidate the mechanism of increased biliary lipid secretion in Bsep−/−mice. The secretion of the BS tauro-β-muricholic acid (TβMCA) is relatively preserved in Bsep−/−mice. We infused Bsep−/−and Bsep+/+(control) mice with TβMCA in stepwise increasing dosages (150–600 nmol/min) and determined biliary bile flow, BS, PL, and CH secretion. mRNA and protein expression of relevant canalicular transporters was analyzed in livers from noninfused Bsep−/−and control mice. TβMCA infusion increased BS secretion in both Bsep−/−and control mice. The secreted PL or CH amount per BS, i.e., the “coupling,” was continuously two- to threefold higher in Bsep−/−mice ( P < 0.05). Hepatic mRNA expression of canalicular lipid transporters Mdr2, Abcg5, and Abcg8 was 45–55% higher in Bsep−/−mice (Abcg5; P < 0.05), as was canalicular Mdr2 and Abcg5 protein expression. Potential other explanations for the increased coupling of the biliary secretion of PL and CH to that of BS in Bsep−/−mice could be excluded. We conclude that the mechanism of increased biliary lipid secretion in Bsep−/−mice is based on increased expression of the responsible canalicular transporter proteins.

Prediction of drug-induced intrahepatic cholestasis:in vitroscreening and QSAR analysis ofdrugs inhibiting the human bile salt export pump

2006 ◽  
Vol 6 (1) ◽  
pp. 71-86 ◽  
Author(s):  
Aki Sakurai ◽  
Atsuo Kurata ◽  
Yuko Onishi ◽  
Hiroyuki Hirano ◽  
Toshihisa Ishikawa
Keyword(s):  
Bile Salt ◽  
Bile Salt Export Pump ◽  
Drug Induced ◽  
Human Bile ◽  
Qsar Analysis

scholarly journals Heterologous Overexpression and Mutagenesis of the Human Bile Salt Export Pump (ABCB11) Using DREAM (Directed REcombination-Assisted Mutagenesis)

PLoS ONE ◽  
2011 ◽  
Vol 6 (5) ◽  
pp. e20562 ◽  
Author(s):  
Jan Stindt ◽  
Philipp Ellinger ◽  
Claudia Stross ◽  
Verena Keitel ◽  
Dieter Häussinger ◽  
...  
Keyword(s):  
Bile Salt ◽  
Bile Salt Export Pump ◽  
Human Bile ◽  
Heterologous Overexpression

scholarly journals Polymorphic variants in the human bile salt export pump (BSEP; ABCB11): functional characterization and interindividual variability

2010 ◽  
Vol 20 (1) ◽  
pp. 45-57 ◽  
Author(s):  
Richard H. Ho ◽  
Brenda F. Leake ◽  
Dawn M. Kilkenny ◽  
Henriette E. Meyer zu Schwabedissen ◽  
Hartmut Glaeser ◽  
...  
Keyword(s):  
Bile Salt ◽  
Interindividual Variability ◽  
Functional Characterization ◽  
Bile Salt Export Pump ◽  
Human Bile ◽  
Polymorphic Variants
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