Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Stumptner, C; Fuchsbichler, A; Lehner, M; Zatloukal, K; Denk, H.
Sequence of events in the assembly of Mallory body components in mouse liver: clues to the pathogenesis and significance of Mallory body formation.
J Hepatol. 2001; 34(5):665-675
Doi: 10.1016%2FS0168-8278%2800%2900099-4
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- Führende Autor*innen der Med Uni Graz
- Denk Helmut
- Stumptner Cornelia
- Co-Autor*innen der Med Uni Graz
- Zatloukal Kurt
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- Abstract:
- BACKGROUND/AIMS: Chronic intoxication of mice with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or griseofulvin (GF) results in appearance of Mallory bodies (MBs) and alterations of the keratin cytoskeleton, which are reversible upon drug withdrawal but recur after readministration within 2-3 days. METHODS: DDC- or GF-treated and recovered mice were reintoxicated with the original drugs but also colchicine and lumicolchicine. Cytoskeletal alterations of hepatocytes and MB formation were monitored by immunofluorescence microscopy using keratin, MB-specific antibodies, antibodies to phosphoepitopes and to HSP70. Keratin 8/18 mRNA expression and protein levels were determined by competitive reverse transcription-polymerase chain reaction, in situ-hybridization and western blotting. RESULTS: Duration of pretreatment was important for the efficiency of MB triggering. Rapid increase of keratin 8/18 mRNA and proteins was found in all reintoxicated mice concomitant with MB formation, whereby keratin 8 prevailed over keratin 18. Keratins and a protein with heat shock characteristics (M(M) 120-1 antigen) were the earliest detectable MB components, whereas ubiquitination and phosphorylation followed later. CONCLUSIONS: Overproduction of keratins is a major but not the only step responsible for MB formation. Additional components (e.g. M(M) 120-1 antigen) and excess of keratin 8 over keratin 18 are essential.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antigens, Surface - pharmacology
- Colchicine - pharmacology
- Dicarbethoxydihydrocollidine - poisoning
- Griseofulvin - poisoning
- Immunohistochemistry - poisoning
- Inclusion Bodies - physiology
- Keratin-8 - physiology
- Keratins - genetics
- Liver - drug effects
- Lumicolchicines - pharmacology
- Male - pharmacology
- Mice - pharmacology
- Phosphorylation - pharmacology
- RNA, Messenger - metabolism
- Time Factors - metabolism
- Ubiquitin - metabolism
- Find related publications in this database (Keywords)
- Mallory body
- griseofulvin
- intermediate filaments
- alcoholic hepatitis
- cytokeratin
- heat shock protein