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SHR Neuro Krebs Kardio Lipid

Marschall, HU; Wagner, M; Bodin, K; Zollner, G; Fickert, P; Gumhold, J; Silbert, D; Fuchsbichler, A; Sjövall, J; Trauner, M.
Fxr(-/-) mice adapt to biliary obstruction by enhanced phase I detoxification and renal elimination of bile acids.
J Lipid Res. 2006; 47(3):582-592 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Fickert Peter
Silbert-Wagner Dagmar
Sommer Judith
Trauner Michael
Wagner Martin
Zollner Gernot
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Abstract:
Farnesoid X receptor knockout (Fxr(-/-)) mice cannot upregulate the bile salt export pump in bile acid loading or cholestatic conditions. To investigate whether Fxr(-/-) mice differ in bile acid detoxification compared with wild-type mice, we performed a comprehensive analysis of bile acids extracted from liver, bile, serum, and urine of naive and common bile duct-ligated wild-type and Fxr(-/-) mice using electrospray and gas chromatography mass spectrometry. In addition, hepatic and renal gene expression levels of Cyp2b10 and Cyp3a11, and protein expression levels of putative renal bile acid-transporting proteins, were investigated. We found significantly enhanced hepatic bile acid hydroxylation in Fxr(-/-) mice, in particular hydroxylations of cholic acid in the 1beta, 2beta, 4beta, 6alpha, 6beta, 22, or 23 position and a significantly enhanced excretion of these metabolites in urine. The gene expression level of Cyp3a11 was increased in the liver of Fxr(-/-) mice, whereas the protein expression levels of multidrug resistance-related protein 4 (Mrp4) were increased in kidneys of both genotypes during common bile duct ligation. In conclusion, Fxr(-/-) mice detoxify accumulating bile acids in the liver by enhanced hydroxylation reactions probably catalyzed by Cyp3a11. The metabolites formed were excreted into urine, most likely with the participation of Mrp4.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Aryl Hydrocarbon Hydroxylases - metabolism
Bile Acids and Salts - blood Bile Acids and Salts - metabolism
Carrier Proteins - metabolism
Cholestasis - metabolism Cholestasis - physiopathology
Cytochrome P-450 CYP3A - metabolism
DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism
Kidney - metabolism
Liver - metabolism
Membrane Glycoproteins - metabolism
Membrane Proteins - metabolism
Metabolic Detoxication, Phase I -
Mice -
Mice, Inbred C57BL - genetics Mice, Inbred C57BL - metabolism
Mice, Knockout -
Multidrug Resistance-Associated Proteins - metabolism
RNA, Messenger - metabolism
Receptors, Cytoplasmic and Nuclear -
Steroid Hydroxylases - metabolism
Transcription Factors - genetics Transcription Factors - metabolism

Find related publications in this database (Keywords)
farnesoid X receptor knockout
multidrug resistance-related protein 4
cytochrome 3a11
gas chromatography-mass spectrometry
electrospray mass spectrometry
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