ArticleThe American journal of pathology2000
Hepatocyte cytokeratins are hyperphosphorylated at multiple sites in human alcoholic hepatitis and in a mallory body mouse model.
Article in The American journal of pathology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 92 citations in OpenAlex.
- Role of SQSTM1/p62 in regulating Mallory-Denk body in alcohol-associated liver disease.eGastroenterology · 2025Article
- What are the common downstream molecular events between alcoholic and nonalcoholic fatty liver?Lipids in health and disease · 2024Review
- Revealing the Roles of Keratin 8/18-Associated Signaling Proteins Involved in the Development of Hepatocellular Carcinoma.International journal of molecular sciences · 2021Review
- Gold Nanorod Photothermal Therapy Alters Cell Junctions and Actin Network in Inhibiting Cancer Cell Collective Migration.ACS nano · 2018Article
- Autophagy in the liver: functions in health and disease.Nature reviews. Gastroenterology & hepatology · 2017Review
- A Mechanistic Review of Cell Death in Alcohol-Induced Liver Injury.Alcoholism, clinical and experimental research · 2016Review
- Pathology of Alcoholic Liver Disease.Journal of clinical and translational hepatology · 2014Review
- Keratin 8 phosphorylation regulates its transamidation and hepatocyte Mallory-Denk body formation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012Article
- Keratin 8 phosphorylation regulates keratin reorganization and migration of epithelial tumor cells.Journal of cell science · 2012Article
- Keratin 18 phosphorylation as a progression marker of chronic hepatitis B.Virology journal · 2010Article
- A cell culture system for the induction of Mallory bodies: Mallory bodies and aggresomes represent different types of inclusion bodies.Histochemistry and cell biology · 2009Article
- Insights into the mechanical properties of epithelial cells: the effects of shear stress on the assembly and remodeling of keratin intermediate filaments.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2009Article
- Intermediate filament cytoskeleton of the liver in health and disease.Histochemistry and cell biology · 2008Review
- p38 MAPK-dependent shaping of the keratin cytoskeleton in cultured cells.The Journal of cell biology · 2007Article
- Increased oxidation and degradation of cytosolic proteins in alcohol-exposed mouse liver and hepatoma cells.Proteomics · 2006Article
- Keratin 8 overexpression promotes mouse Mallory body formation.The Journal of cell biology · 2005Article
- Heat shock protein 70 expression, keratin phosphorylation and Mallory body formation in hepatocytes from griseofulvin-intoxicated mice.Comparative hepatology · 2004Article
- Keratins modulate c-Flip/extracellular signal-regulated kinase 1 and 2 antiapoptotic signaling in simple epithelial cells.Molecular and cellular biology · 2004Article
- Phosphorylation state-specific antibodies: applications in investigative and diagnostic pathology.The American journal of pathology · 2003Review
- Bile acid-induced Mallory body formation in drug-primed mouse liver.The American journal of pathology · 2002Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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