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Fructose protects murine hepatocytes from tumor necrosis factor-induced apoptosis by modulating JNK signaling

Fructose protects murine hepatocytes from tumor necrosis factor-induced apoptosis by modulating JNK signaling

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SPEICHER, Tobias, Ulrike A. KÖHLER, Alexander CHOUKÈR, Sabine WERNER, Timo WEILAND, Albrecht WENDEL, 2012. Fructose protects murine hepatocytes from tumor necrosis factor-induced apoptosis by modulating JNK signaling. In: Journal of Biological Chemistry. 287(3), pp. 1837-1846. ISSN 0021-9258. eISSN 1083-351X

@article{Speicher2012-01-13Fruct-23564, title={Fructose protects murine hepatocytes from tumor necrosis factor-induced apoptosis by modulating JNK signaling}, year={2012}, doi={10.1074/jbc.M111.266742}, number={3}, volume={287}, issn={0021-9258}, journal={Journal of Biological Chemistry}, pages={1837--1846}, author={Speicher, Tobias and Köhler, Ulrike A. and Choukèr, Alexander and Werner, Sabine and Weiland, Timo and Wendel, Albrecht} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/23564"> <dc:contributor>Werner, Sabine</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-06-11T14:21:03Z</dc:date> <dcterms:bibliographicCitation>The Journal of Biological Chemistry ; 287 (2012), 3. - S. 1837-1846</dcterms:bibliographicCitation> <dc:creator>Weiland, Timo</dc:creator> <dc:creator>Speicher, Tobias</dc:creator> <dc:contributor>Wendel, Albrecht</dc:contributor> <dc:creator>Werner, Sabine</dc:creator> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/23564"/> <dcterms:issued>2012-01-13</dcterms:issued> <dcterms:title>Fructose protects murine hepatocytes from tumor necrosis factor-induced apoptosis by modulating JNK signaling</dcterms:title> <dc:contributor>Weiland, Timo</dc:contributor> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-06-11T14:21:03Z</dcterms:available> <dc:creator>Choukèr, Alexander</dc:creator> <dc:language>eng</dc:language> <dc:rights>deposit-license</dc:rights> <dc:contributor>Choukèr, Alexander</dc:contributor> <dcterms:abstract xml:lang="eng">Fructose-induced hepatic ATP depletion prevents TNF-induced apoptosis, whereas it contrarily enhances CD95-induced hepatocyte apoptosis in vitro and in vivo. By contrast, transformed liver cells are not protected against TNF due to metabolic alterations, allowing selective tumor targeting. We analyzed the molecular mechanisms by which fructose modulates cytokine-induced apoptosis. A release of adenosine after fructose-induced ATP depletion, followed by a cAMP response, was demonstrated. Likewise, cAMP and adenosine mimicked per se the modulation by fructose of CD95- and TNF-induced apoptosis. The effects of fructose on cytokine-induced apoptosis were sensitive to inhibition of protein kinase A. Fructose prevented the pro-apoptotic, sustained phase of TNF-induced JNK signaling and thereby blocked bid-mediated activation of the intrinsic mitochondrial apoptosis pathway in a PKA-dependent manner. We explain the dichotomal effects of fructose on CD95- and TNF-induced cell death by the selective requirement of JNK signaling for the latter. These findings provide a mechanistic rationale for the protection of hepatocytes from TNF-induced cell death by pharmacological doses of fructose.</dcterms:abstract> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103605204-4002607-1"/> <dc:creator>Wendel, Albrecht</dc:creator> <dc:contributor>Speicher, Tobias</dc:contributor> <dc:contributor>Köhler, Ulrike A.</dc:contributor> <dc:creator>Köhler, Ulrike A.</dc:creator> </rdf:Description> </rdf:RDF>

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