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Fickert, P; Trauner, M; Fuchsbichler, A; Zollner, G; Wagner, M; Marschall, HU; Zatloukal, K; Denk, H.
Oncosis represents the main type of cell death in mouse models of cholestasis.
J Hepatol. 2005; 42(3):378-385
Doi: 10.1016/j.jhep.2004.10.016
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- Führende Autor*innen der Med Uni Graz
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Fickert Peter
- Co-Autor*innen der Med Uni Graz
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Denk Helmut
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Trauner Michael
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Wagner Martin
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Zatloukal Kurt
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Zollner Gernot
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- Abstract:
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Since the mechanisms leading to hepatocyte death in cholestasis are not well defined, we aimed to obtain closer insights into the related pathogenetic principles.
Cell death was assessed in common bile duct ligated (CBDL) and cholic acid (CA)-fed mice, and compared to Fas agonist Jo2-injected mice by studying H and E-stained tissue sections, DNA ladder analysis, caspase-3-like activity assay, immunohistochemistry, double immunofluorescence microscopy for activated caspase-3 and cytokeratin (CK) 18, the TUNEL method, and electron microscopy.
Jo2-treated mice showed activation of caspase-3, breakdown of the CK intermediate filament network, and classical morphological features of apoptosis. In contrast, in CA-fed and CBDL mice, oncosis characterized by cell swelling and ruptured cell membranes was the predominant type of cell death, whereas in both experimental conditions significant activation of caspase-3 was absent and typical CK alterations were rare despite frequent positivity of the TUNEL assay.
(i) Oncosis represents the main type of hepatocyte death in acute cholestasis in mice. (ii) The importance of apoptosis in cholestasis may be overestimated if non-specific detection systems (e.g. TUNEL assay) are used.
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Animals -
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Apoptosis -
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Aspartate Aminotransferases - blood
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Bile Acids and Salts - blood
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Bile Ducts - physiology
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Cell Death -
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Cell Membrane - pathology
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Cholestasis - pathology
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Cholic Acid - toxicity
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Disease Models, Animal -
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Hepatocytes - pathology Hepatocytes - ultrastructure
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Male -
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Mice -
- Find related publications in this database (Keywords)
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apoptosis
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bile acids
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bile duct ligation
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cholestatic liver injury
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cholic acid
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hepatic artery
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necrosis
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obstructive jaundice