Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid

Wagner, M; Zollner, G; Fickert, P; Gumhold, J; Silbert, D; Fuchsbichler, A; Gujral, JS; Zatloukal, K; Denk, H; Jaeschke, H; Trauner, M.
Hepatobiliary transporter expression in intercellular adhesion molecule 1 knockout and Fas receptor-deficient mice after common bile duct ligation is independent of the degree of inflammation and oxidative stress.
Drug Metab Dispos. 2007; 35(9):1694-1699 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Denk Helmut
Fickert Peter
Silbert-Wagner Dagmar
Sommer Judith
Trauner Michael
Wagner Martin
Zatloukal Kurt
Zollner Gernot

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Plum Analytics:
Liver injury in intercellular adhesion molecule 1 knockout (ICAM(-/-)) and Fas receptor-deficient (lpr) mice is markedly reduced after common bile duct ligation (CBDL) due to significantly reduced inflammation and oxidative stress. Liver injury in CBDL rodents is counteracted by adaptive hepatobiliary transporter induction. Since hepatobiliary transporter expression in obstructive cholestasis may be regulated not only by accumulating bile acids but also by inflammatory mediators and oxidative stress, we hypothesized that differences in the inflammatory response may affect hepatobiliary transporter expression in CBDL, which would contribute to reduced liver injury. Therefore, expression of major hepatobiliary transporters (Ntcp, Bsep, Mrp2-4, Ost alpha/beta) was determined by Taqman RT-PCR and Western blotting in sham-operated animals and 3 days after CBDL in wild-type, ICAM(-/-) and lpr mice of the endotoxin-sensitive C57BL/6 and the endotoxin-resistant C3H/HeJ strains. CBDL resulted in a significant decrease of Ntcp in all genotypes. Canalicular transporters Bsep and Mrp2 were repressed only in the endotoxin-sensitive strain regardless of the genotype. Mrp3 was moderately induced in ICAM(-/-), lpr, and endotoxin-resistant mice, whereas Mrp4 was only induced in the endotoxin-resistant strain. Ost beta was massively induced in all CBDL mice, whereas Ost alpha was reduced. In conclusion, markedly reduced inflammation and oxidative stress in CBDL ICAM(-/-) and lpr mice does not profoundly affect hepatobiliary transporter expression. Therefore, transporter expression does not account for reduced liver injury in ICAM(-/-) and lpr mice. Induction of the adaptive transporter response after CBDL is independent of the degree of the inflammatory response. Rather, retention of biliary constituents may determine transporter expression in CBDL.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Antigens, CD95 - deficiency Antigens, CD95 - genetics
Bile - metabolism
Bile Canaliculi - metabolism
Blotting, Western -
Carrier Proteins - metabolism
Common Bile Duct - metabolism Common Bile Duct - physiology
Endotoxins - toxicity
Inflammation - metabolism
Intercellular Adhesion Molecule-1 - genetics
Liver - metabolism
Mice -
Mice, Inbred C3H -
Mice, Inbred C57BL -
Mice, Knockout -
Oxidative Stress - physiology
RNA - biosynthesis RNA - genetics
Reverse Transcriptase Polymerase Chain Reaction -

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