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Selected Publication:
Zatloukal, K; Stumptner, C; Lehner, M; Denk, H; Baribault, H; Eshkind, LG; Franke, WW.
Cytokeratin 8 protects from hepatotoxicity, and its ratio to cytokeratin 18 determines the ability of hepatocytes to form Mallory bodies.
Am J Pathol. 2000; 156(4):1263-1274
Doi: 10.1016/S0002-9440(10)64997-8
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- Leading authors Med Uni Graz
- Zatloukal Kurt
- Co-authors Med Uni Graz
- Denk Helmut
- Stumptner Cornelia
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- Abstract:
- In alcoholic hepatitis, a severe form of alcohol-induced toxic liver injury, as well as in experimental intoxication of mice with the porphyrinogenic drugs griseofulvin and 3,5-diethoxycarbonyl-1, 4-dihydrocollidine, hepatocytes form cytoplasmic protein aggregates (Mallory bodies; MBs) containing cytokeratins (CKs) and non-CK components. Here we report that mice lacking the CK8 gene and hence CK intermediate filaments in hepatocytes, but still expressing the type I partner, ie, the CK18 gene, do not form MBs but suffer from extensive porphyria and progressive toxic liver damage, leading to the death of a considerable number of animals (7 of 12 during 12 weeks of intoxication). Our observations show that 1) in the absence of CK8 as well as in the situation of a relative excess of CK18 over CK8 no MBs are formed; 2) the loss of CK8 is not compensated by other type II CKs; and 3) porphyria and toxic liver damage are drastically enhanced in the absence of CK8. Our results point to a protective role of CKs in certain types of toxic liver injury and suggest that MBs by themselves are not harmful to hepatocytes but may be considered as a product of a novel defense mechanism in hepatocytes.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Bile Ducts - physiology
- Cytoplasm - physiology
- Cytoskeleton - ultrastructure
- Dicarbethoxydihydrocollidine - ultrastructure
- Epithelium - physiology
- Keratin-7 - physiology
- Keratins - genetics
- Liver - cytology
- Liver Diseases - chemically induced
- Mice - chemically induced
- Mice, Inbred Strains - chemically induced
- Mice, Knockout - genetics