Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Fickert, P; Zollner, G; Fuchsbichler, A; Stumptner, C; Pojer, C; Zenz, R; Lammert, F; Stieger, B; Meier, PJ; Zatloukal, K; Denk, H; Trauner, M.
Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver.
Gastroenterology. 2001; 121(1):170-183
Doi: 10.1053/gast.2001.25542
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- Führende Autor*innen der Med Uni Graz
- Fickert Peter
- Trauner Michael
- Co-Autor*innen der Med Uni Graz
- Denk Helmut
- Pein Christine
- Stumptner Cornelia
- Zatloukal Kurt
- Zollner Gernot
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- Abstract:
- Background & Aims: Cholestasis is associated with retention of potentially toxic bile acids and alterations in hepatocellular transporter expression. Conversely, nontoxic ursodeoxycholic acid (UDCA) stimulates bile secretion and counteracts cholestasis. This study aimed to determine the effects of UDCA and cholic acid (CA) on the expression of hepatocellular transporters for bile acids (Ntcp, Bsep), organic anions (Oatp1, Mrp2), organic cations (Mdr1a/b), and phospholipids (Mdr2) in mouse liver. Methods: Bile flow/composition was analyzed in UDCA- or CA-fed mice. Transporter expression was studied by reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence microscopy. Results: UDCA had no effect on basolateral Ntcp and down-regulated Oatp1, whereas canalicular Bsep and Mrp2 were up-regulated. CA down-regulated basolateral Ntcp and Oatp1, whereas canalicular Bsep, Mrp2, and Mdr1a/b were up-regulated. Neither UDCA nor CA affected Mdr2 expression. Both UDCA and CA stimulated biliary bile acid and glutathione excretion, although only CA increased phospholipid and cholesterol excretion. Conclusions: Down-regulation of basolateral and up-regulation of canalicular transporters in response to CA may represent a defense mechanism, in an attempt to prevent hepatocellular accumulation of potentially toxic bile acids. The therapeutic effects of UDCA may be caused in part by stimulation of canalicular transporter expression in the absence of hepatocellular toxicity.
- Find related publications in this database (using NLM MeSH Indexing)
- Administration, Oral -
- Animals -
- Bile Acids and Salts - secretion
- Bile Ducts - metabolism
- Biological Transport - drug effects
- Cholic Acid - administration and dosage Cholic Acid - pharmacology
- Down-Regulation - drug effects
- Gene Expression Regulation - drug effects
- Liver - drug effects Liver - metabolism Liver - pathology
- Male -
- Mice -
- Reverse Transcriptase Polymerase Chain Reaction -
- Up-Regulation - drug effects
- Ursodeoxycholic Acid - administration and dosage Ursodeoxycholic Acid - pharmacology