Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Stumptner, C; Omary, MB; Fickert, P; Denk, H; Zatloukal, K.
Hepatocyte cytokeratins are hyperphosphorylated at multiple sites in human alcoholic hepatitis and in a mallory body mouse model.
Am J Pathol. 2000; 156(1):77-90
Doi: 10.1016/S0002-9440(10)64708-6
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- Führende Autor*innen der Med Uni Graz
- Stumptner Cornelia
- Zatloukal Kurt
- Co-Autor*innen der Med Uni Graz
- Denk Helmut
- Fickert Peter
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- Abstract:
- Alcoholic hepatitis (AH) is associated with cytokeratin 8 and 18 (CK8/18) accumulation as cytoplasmic inclusion bodies, termed Mallory bodies (MBs). Studies with MB mouse models and cultured hepatocytes suggested that CK8/18 hyperphosphorylation might be involved in MB formation. However, no data exist on phosphorylation of CK8/18 in human AH. In this study, antibodies that selectively recognize phosphorylated epitopes of CK8 or CK18 were used to analyze CK8/18 phosphorylation states in normal human and murine livers, human AH biopsies, and livers of 3,5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC)-intoxicated mice, the last serving as model for MB induction. Hepatocyte cytokeratins become hyperphosphorylated at multiple sites in AH and in DDC-intoxicated mice. Hyperphosphorylation of CK8/18 occurred rapidly, after 1 day of DDC intoxication and preceded architectural changes of the cytoskeleton. In long-term DDC-intoxicated mice as well as in human AH, MBs preferentially contain hyperphosphorylated CK8/18 as compared with the cytoplasmic cytokeratin intermediate filament network suggesting that CK8/18 hyperphosphorylation may play a contributing role in MB pathogenesis. Furthermore, the site-specific phosphorylation of cytokeratin in different stages of MB induction provides indirect evidence for the involvement of a variety of protein kinases known to be activated in stress responses, mitosis, and apoptosis.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Dicarbethoxydihydrocollidine - poisoning
- Hepatitis, Alcoholic - metabolism Hepatitis, Alcoholic - pathology
- Humans -
- Inclusion Bodies - metabolism
- Keratins - metabolism
- Liver - metabolism Liver - pathology
- Male -
- Mice -
- Phosphorylation -