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Tumor necrosis factor alpha sensitizes primary murine hepatocytes to Fas/CD95-mediated apoptosis in a Bim and Bid-dependent manner

Tumor necrosis factor alpha sensitizes primary murine hepatocytes to Fas/CD95-mediated apoptosis in a Bim and Bid-dependent manner

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SCHMICH, Kathrin, Rebekka SCHLATTER, Nadia CORAZZA, Karine SÁ FERREIRA, Michael EDERER, Thomas BRUNNER, Christoph BORNER, Irmgard MERFORT, 2011. Tumor necrosis factor alpha sensitizes primary murine hepatocytes to Fas/CD95-mediated apoptosis in a Bim and Bid-dependent manner. In: Hepatology. 53(1), pp. 282-292. ISSN 0270-9139. eISSN 1527-3350. Available under: doi: 10.1002/hep.23987

@article{Schmich2011-01Tumor-14237, title={Tumor necrosis factor alpha sensitizes primary murine hepatocytes to Fas/CD95-mediated apoptosis in a Bim and Bid-dependent manner}, year={2011}, doi={10.1002/hep.23987}, number={1}, volume={53}, issn={0270-9139}, journal={Hepatology}, pages={282--292}, author={Schmich, Kathrin and Schlatter, Rebekka and Corazza, Nadia and Sá Ferreira, Karine and Ederer, Michael and Brunner, Thomas and Borner, Christoph and Merfort, Irmgard} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/14237"> <dc:creator>Schlatter, Rebekka</dc:creator> <dc:contributor>Corazza, Nadia</dc:contributor> <dc:creator>Ederer, Michael</dc:creator> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:creator>Brunner, Thomas</dc:creator> <dc:creator>Merfort, Irmgard</dc:creator> <dc:contributor>Schlatter, Rebekka</dc:contributor> <dc:creator>Corazza, Nadia</dc:creator> <dc:rights>deposit-license</dc:rights> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-07-27T06:59:21Z</dcterms:available> <dcterms:bibliographicCitation>First publ. in: Hepatology ; 53 (2011), 1. - S. 282–292</dcterms:bibliographicCitation> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/14237"/> <dcterms:abstract xml:lang="eng">Fas/CD95 is a critical mediator of cell death in many chronic and acute liver diseases and induces apoptosis in primary hepatocytes in vitro. In contrast, the pro inflammatory cytokine tumor necrosis factor alpha (TNFalpha) fails to provoke cell death in isolated hepatocytes but has been implicated in hepatocyte apoptosis during liver diseases associated with chronic inflammation. Here we report that TNFalpha sensitizes primary murine hepatocytes cultured on collagen to Fas ligand (FasL)-induced apoptosis. This synergism is time-dependent and is specifically mediated by TNFalpha. Fas itself is essential for the sensitization, but neither Fas up-regulation nor endogenous FasL is responsible for this effect. Although FasL is shown to induce Bid-independent apoptosis in hepatocytes cultured on collagen, the sensitizing effect of TNFalpha is clearly dependent on Bid. Moreover, both c-Jun N-terminal kinase ONK) activation and Bim, another B cell lymphoma 2 homology domain 3 (BH3)-only protein, are crucial mediators of TNFalpha-induced apoptosis sensitization. Bim and Bid activate the mitochondrial amplification loop and induce cytochrome c release, a hallmark of type II apoptosis. The mechanism of TNFalpha-induced sensitization is supported by a mathematical model that correctly reproduces the biological findings. Finally, our results are physiologically relevant because TNFalpha also sensitizes to agonistic anti-Fas-induced liver damage. Conclusion: Our data suggest that TNFIX can cooperate with FasL to induce hepatocyte apoptosis by activating the BH3-only proteins Bim and Bid.</dcterms:abstract> <dc:creator>Schmich, Kathrin</dc:creator> <dc:language>eng</dc:language> <dc:contributor>Sá Ferreira, Karine</dc:contributor> <dc:creator>Sá Ferreira, Karine</dc:creator> <dc:contributor>Merfort, Irmgard</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-07-27T06:59:21Z</dc:date> <dc:contributor>Brunner, Thomas</dc:contributor> <dc:contributor>Borner, Christoph</dc:contributor> <dc:creator>Borner, Christoph</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dcterms:issued>2011-01</dcterms:issued> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/14237/2/Brunner.pdf"/> <dcterms:title>Tumor necrosis factor alpha sensitizes primary murine hepatocytes to Fas/CD95-mediated apoptosis in a Bim and Bid-dependent manner</dcterms:title> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/14237/2/Brunner.pdf"/> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103605204-4002607-1"/> <dc:contributor>Ederer, Michael</dc:contributor> <dc:contributor>Schmich, Kathrin</dc:contributor> </rdf:Description> </rdf:RDF>

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