The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Van Molle, W.
Right arrow Articles by Libert, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Van Molle, W.
Right arrow Articles by Libert, C.
The Journal of Immunology, 1999, 163: 5235-5241.
Copyright © 1999 by The American Association of Immunologists

Activation of Caspases in Lethal Experimental Hepatitis and Prevention by Acute Phase Proteins1

Wim Van Molle2,*, Geertrui Denecker2,*, Ivan Rodriguez{dagger}, Peter Brouckaert*, Peter Vandenabeele* and Claude Libert3,*

* Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Ghent, Ghent, Belgium; and {dagger} Laboratory of Vertebrate Neurobiology, The Rockefeller University, New York, NY 10021

Lethal hepatitis can be induced by an agonistic anti-Fas Ab in normal mice or by TNF in mice sensitized to D-(+)-galactosamine or actinomycin D. In all three models, we found that apoptosis of hepatocytes is an early and necessary step to cause lethality. In the three models, we observed activation of the major executioner caspases-3 and -7. Two acute-phase proteins, {alpha}1-acid glycoprotein and {alpha}1-antitrypsin, differentially prevent lethality: {alpha}1-acid glycoprotein protects in both TNF models and not in the anti-Fas model, while {alpha}1-antitrypsin confers protection in the TNF/D-(+)-galactosamine model only. The protection is inversely correlated with activation of caspase-3 and caspase-7. The data suggest that activation of caspase-3 and -7 is essential in the in vivo induction of apoptosis leading to lethal hepatitis and that acute phase proteins are powerful inhibitors of apoptosis and caspase activation. Furthermore, Bcl-2 transgenic mice, expressing Bcl-2 specifically in hepatocytes, are protected against a lethal challenge with anti-Fas or with TNF/D-(+)-galactosamine, but not against TNF/actinomycin D. The acute-phase proteins might constitute an inducible anti-apoptotic protective system, which in pathology or disturbed homeostasis prevents excessive apoptosis.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
H.-M. Ni, X. Chen, Y.-H. Shi, Y. Liao, A. A. Beg, J. Fan, and X.-M. Yin
Genetic Delineation of the Pathways Mediated by Bid and JNK in Tumor Necrosis Factor-{alpha}-induced Liver Injury in Adult and Embryonic Mice
J. Biol. Chem., February 13, 2009; 284(7): 4373 - 4382.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
S. Qin, H. Wang, R. Yuan, H. Li, M. Ochani, K. Ochani, M. Rosas-Ballina, C. J. Czura, J. M. Huston, E. Miller, et al.
Role of HMGB1 in apoptosis-mediated sepsis lethality
J. Exp. Med., July 10, 2006; 203(7): 1637 - 1642.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. Van Lint, B. Wielockx, L. Puimege, A. Noel, C. Lopez-Otin, and C. Libert
Resistance of Collagenase-2 (Matrix Metalloproteinase-8)-Deficient Mice to TNF-Induced Lethal Hepatitis
J. Immunol., December 1, 2005; 175(11): 7642 - 7649.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
H. Zhang, J. Taylor, D. Luther, J. Johnston, S. Murray, J. R. Wyatt, A. T. Watt, S. Koo, C. York-DeFalco, K. Stecker, et al.
Antisense Oligonucleotide Inhibition of Bcl-xL and Bid Expression in Liver Regulates Responses in a Mouse Model of Fas-Induced Fulminant Hepatitis
J. Pharmacol. Exp. Ther., October 1, 2003; 307(1): 24 - 33.
[Abstract] [Full Text] [PDF]

Home page
 Innate ImmunityHome page
E. Jirillo, D. Caccavo, T. Magrone, E. Piccigallo, L. Amati, A. Lembo, C. Kalis, and M. Gumenscheimer
Review: The role of the liver in the response to LPS: experimental and clinical findings
Innate Immunity, October 1, 2002; 8(5): 319 - 327.
[Abstract] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
C. Zabel, D. C. Chamrad, J. Priller, B. Woodman, H. E. Meyer, G. P. Bates, and J. Klose
Alterations in the Mouse and Human Proteome Caused by Huntington's Disease
Mol. Cell. Proteomics, May 1, 2002; 1(5): 366 - 375.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
S. Vejda, C. Posovszky, S. Zelzer, B. Peter, E. Bayer, D. Gelbmann, R. Schulte-Hermann, and C. Gerner
Plasma from Cancer Patients Featuring a Characteristic Protein Composition Mediates Protection against Apoptosis
Mol. Cell. Proteomics, May 1, 2002; 1(5): 387 - 393.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
W. Waelput, D. Broekaert, J. Vandekerckhove, P. Brouckaert, J. Tavernier, and C. Libert
A Mediator Role For Metallothionein in Tumor Necrosis Factor-induced Lethal Shock
J. Exp. Med., December 3, 2001; 194(11): 1617 - 1624.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
M. Latta, G. Kunstle, M. Leist, and A. Wendel
Metabolic Depletion of Atp by Fructose Inversely Controls Cd95- and Tumor Necrosis Factor Receptor 1-Mediated Hepatic Apoptosis
J. Exp. Med., June 5, 2000; 191(11): 1975 - 1986.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 1999 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 1999 by The American Association of Immunologists, Inc. All rights reserved.