Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Fickert, P; Trauner, M; Fuchsbichler, A; Stumptner, C; Zatloukal, K; Denk, H.
Cytokeratins as targets for bile acid-induced toxicity.
Am J Pathol. 2002; 160(2):491-499
Doi: 10.1016/S0002-9440(10)64868-7
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- Führende Autor*innen der Med Uni Graz
- Denk Helmut
- Fickert Peter
- Co-Autor*innen der Med Uni Graz
- Stumptner Cornelia
- Trauner Michael
- Zatloukal Kurt
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- Abstract:
- Cholestasis is associated with retention of potentially toxic bile acids and profound cytoskeletal alterations of hepatocytes. Given the well-established cytoprotective role of hepatocyte keratins this study aimed to determine the effects of cholestasis on the cytokeratin (CK) intermediate filament network in mouse liver. Mice were subjected to common bile duct ligation or sham operation. Mice were also fed a cholic acid or ursodeoxycholic acid (UDCA)-supplemented diet (0.1%, 0.5%, and 1%) or control diet for 7 days. CK 8 and CK 18 expression was studied by competitive reverse transcriptase-polymerase chain reaction, in situ hybridization, Western blot analysis, and immunofluorescence microscopy. Common bile duct ligation and cholic acid feeding significantly stimulated CK 8 and CK 18 mRNA and protein levels compared to controls, whereas UDCA had no effect. CK overexpression was accompanied by pronounced phosphorylation. Our results show that potentially toxic bile acids induce hepatocytic CK 8 and CK 18 expression and phosphorylation whereas nontoxic UDCA has no effect on CKs. Thus, increased hepatocellular CK expression and phosphorylation in cholestasis may be caused by retention of toxic bile acids and reflect a hepatocellular stress response with potential beneficial effects.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Bile Acids and Salts - administration and dosage Bile Acids and Salts - toxicity
- Bile Ducts - surgery
- Cholestasis - physiopathology
- Cytoskeleton - metabolism
- Diet -
- Hepatocytes - cytology Hepatocytes - metabolism
- Humans -
- Immunohistochemistry -
- In Situ Hybridization -
- Intermediate Filaments - metabolism
- Keratins - genetics Keratins - metabolism
- Liver - enzymology
- Male -
- Mice -