help button home button Am J Pathol Epitomics Buy 2 Antibodies Get 1 Free Special Offer
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fickert, P.
Right arrow Articles by Denk, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fickert, P.
Right arrow Articles by Denk, H.
(American Journal of Pathology. 2002;161:2019-2026.)
© 2002 American Society for Investigative Pathology

Regular Articles

Bile Acid-Induced Mallory Body Formation in Drug-Primed Mouse Liver

Peter Fickert*, Michael Trauner*, Andrea Fuchsbichler{dagger}, Conny Stumptner{dagger}, Kurt Zatloukal{dagger} and Helmut Denk{dagger}

From the Departments of Medicine* and Pathology,{dagger} Karl-Franzens University, Graz, Austria

Chronic cholestasis is associated with retention of bile acids and profound cytoskeletal alterations in hepatocytes including Mallory body (MB) formation. The mechanisms responsible for MB formation in cholestatic liver diseases are unclear. The aim of our study was to determine the relevance of cholestasis and bile acids for MB formation. For this purpose mice received a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-supplemented diet for 2.5 months to induce MB formation. After recovery from DDC intoxication for 4 weeks followed by disappearance of MBs, these drug-primed mice were subjected to DDC refeeding, common bile duct ligation (CBDL), and feeding of a cholic acid (CA)-supplemented diet for 7 days, respectively. Cytokeratin (CK) 8 and CK 18 expression was studied by competitive reverse transcriptase-polymerase chain reaction and Western blot analysis. Cytoskeletal alterations of hepatocytes and MB formation were monitored by immunofluorescence microscopy and immunohistochemistry using CK-, ubiquitin-, and MB-specific antibodies. Like DDC refeeding, both CBDL and CA feeding of drug-primed mice significantly increased CK 8 and CK 18 mRNA and protein levels (with excess of CK 8) and resulted in ubiquitination and abnormal phosphorylation of CKs. Furthermore, CBDL and CA feeding resulted in rapid neoformation of MBs in drug-primed mice. It is concluded that MB formation in cholestatic liver diseases may be triggered by the action of potentially toxic bile acids.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
P. Fickert, U. Stoger, A. Fuchsbichler, T. Moustafa, H.-U. Marschall, A. H. Weiglein, O. Tsybrovskyy, H. Jaeschke, K. Zatloukal, H. Denk, et al.
A New Xenobiotic-Induced Mouse Model of Sclerosing Cholangitis and Biliary Fibrosis
Am. J. Pathol., August 1, 2007; 171(2): 525 - 536.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
G. Zollner, M. Wagner, P. Fickert, A. Geier, A. Fuchsbichler, D. Silbert, J. Gumhold, K. Zatloukal, A. Kaser, H. Tilg, et al.
Role of nuclear receptors and hepatocyte-enriched transcription factors for Ntcp repression in biliary obstruction in mouse liver
Am J Physiol Gastrointest Liver Physiol, November 1, 2005; 289(5): G798 - G805.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
D. Dinsdale, J. C. Lee, G. Dewson, G. M. Cohen, and M. E. Peter
Intermediate Filaments Control the Intracellular Distribution of Caspases During Apoptosis
Am. J. Pathol., February 1, 2004; 164(2): 395 - 407.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by the American Society for Investigative Pathology.