Type of Publication: | Journal article |
URI (citable link): | http://nbn-resolving.de/urn:nbn:de:bsz:352-142340 |
Author: | Badmann, Anastasia; Keough, Adrian; Kaufmann, Thomas; Bouillet, Philippe; Brunner, Thomas; Corazza, Nadia |
Year of publication: | 2011 |
Published in: | Cell Death and Disease ; 2 (2011), 6. - e171. - eISSN 2041-4889 |
Pubmed ID: | 21654829 |
DOI (citable link): | https://dx.doi.org/10.1038/cddis.2011.55 |
Summary: |
Acetaminophen (N-acetyl-para-aminophenol (APAP), paracetamol) is a commonly used analgesic and antipyretic agent. Although considered safe at therapeutic doses, accidental or intentional overdose causes acute liver failure characterized by centrilobular hepatic necrosis with high morbidity and mortality. Although many molecular aspects of APAP-induced cell death have been described, no conclusive mechanism has been proposed. We recently identified TNF-related apoptosis-inducing ligand (TRAIL) and c-Jun kinase(JNK)-dependent activation of the pro-apoptotic Bcl-2 homolog Bim as an important apoptosis amplification pathway in hepatocytes. In this study, we, thus, investigated the role of TRAIL, c-JNK and Bim in APAP-induced liver damage. Our results demonstrate that TRAIL strongly synergizes with APAP in inducing cell death in hepatocyte-like cells lines and primary hepatocyte. Furthermore, we found that APAP strongly induces the expression of Bim in a c-JNK-dependent manner. Consequently, TRAIL- or Bim-deficient mice were substantially protected from APAP-induced liver damage. This study
identifies the TRAIL-JNK-Bim axis as a novel target in the treatment of APAP-induced liver damage and substantiates its general role in hepatocyte death. |
Subject (DDC): | 570 Biosciences, Biology |
Keywords: | Hepatocytes, Jun kinase, Death receptor signaling, Bcl-2 family, Paracetamol |
Link to License: | In Copyright |
Bibliography of Konstanz: | Yes |
BADMANN, Anastasia, Adrian KEOUGH, Thomas KAUFMANN, Philippe BOUILLET, Thomas BRUNNER, Nadia CORAZZA, 2011. Role of TRAIL and the pro-apoptotic Bcl-2 homolog Bim in acetaminophen-induced liver damage. In: Cell Death and Disease. 2(6), e171. eISSN 2041-4889. Available under: doi: 10.1038/cddis.2011.55
@article{Badmann2011TRAIL-14234, title={Role of TRAIL and the pro-apoptotic Bcl-2 homolog Bim in acetaminophen-induced liver damage}, year={2011}, doi={10.1038/cddis.2011.55}, number={6}, volume={2}, journal={Cell Death and Disease}, author={Badmann, Anastasia and Keough, Adrian and Kaufmann, Thomas and Bouillet, Philippe and Brunner, Thomas and Corazza, Nadia}, note={Article Number: e171} }
Badmann_Role-Of-Trail.pdf | 696 |