Intracellular nicotinamide adenine dinucleotide promotes TNF-induced necroptosis in a sirtuin-dependent manner
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| Titel: | Intracellular nicotinamide adenine dinucleotide promotes TNF-induced necroptosis in a sirtuin-dependent manner |
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| Autoren: | Preyat, Nicolas, Rossi, M., Kers, J, Chen, L, Bertin, J, Gough, P J, Le Moine, Alain, Rongvaux, Anthony, Van Gool, Frédéric, Leo, Oberdan |
| Quelle: | Cell Death & Differentiation. 23:29-40 |
| Verlagsinformationen: | Springer Science and Business Media LLC, 2015. |
| Publikationsjahr: | 2015 |
| Schlagwörter: | 0301 basic medicine, Cytoplasm, Fas Ligand Protein, Necrosis -- genetics -- metabolism, Apoptosis, Sirtuin 2 -- genetics -- metabolism, Ligands, Tumor Necrosis Factor-alpha -- genetics -- metabolism, Cell Line, Necrosis, 03 medical and health sciences, Sirtuins -- genetics -- metabolism, Sirtuin 2, Humans, Sirtuins, Fas Ligand Protein -- genetics -- metabolism, 0303 health sciences, Apoptosis -- genetics, Tumor Necrosis Factor-alpha, Sciences bio-médicales et agricoles, NAD -- genetics -- metabolism, NAD, 3. Good health, Cytoplasm -- metabolism, Receptor-Interacting Protein Serine-Threonine Kinases, Receptor-Interacting Protein Serine-Threonine Kinases -- genetics -- metabolism |
| Beschreibung: | Cellular necrosis has long been regarded as an incidental and uncontrolled form of cell death. However, a regulated form of cell death termed necroptosis has been identified recently. Necroptosis can be induced by extracellular cytokines, pathogens and several pharmacological compounds, which share the property of triggering the formation of a RIPK3-containing molecular complex supporting cell death. Of interest, most ligands known to induce necroptosis (including notably TNF and FASL) can also promote apoptosis, and the mechanisms regulating the decision of cells to commit to one form of cell death or the other are still poorly defined. We demonstrate herein that intracellular nicotinamide adenine dinucleotide (NAD(+)) has an important role in supporting cell progression to necroptosis. Using a panel of pharmacological and genetic approaches, we show that intracellular NAD(+) promotes necroptosis of the L929 cell line in response to TNF. Use of a pan-sirtuin inhibitor and shRNA-mediated protein knockdown led us to uncover a role for the NAD(+)-dependent family of sirtuins, and in particular for SIRT2 and SIRT5, in the regulation of the necroptotic cell death program. Thus, and in contrast to a generally held view, intracellular NAD(+) does not represent a universal pro-survival factor, but rather acts as a key metabolite regulating the choice of cell demise in response to both intrinsic and extrinsic factors. |
| Publikationsart: | Article |
| Dateibeschreibung: | 1 full-text file(s): application/pdf |
| Sprache: | English |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/cdd.2015.60 |
| Zugangs-URL: | https://europepmc.org/articles/pmc4815976?pdf=render https://pubmed.ncbi.nlm.nih.gov/26001219 https://www.narcis.nl/publication/RecordID/oai%3Apure.amc.nl%3Apublications%2F42adae53-195e-4e57-8fab-66ca83786b56 https://difusion.ulb.ac.be/vufind/Record/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/199892/Details https://pubmed.ncbi.nlm.nih.gov/26001219/ https://www.nature.com/articles/cdd201560 https://core.ac.uk/display/77565096 https://www.nature.com/articles/cdd201560.pdf https://pure.amsterdamumc.nl/en/publications/e6dcc352-8561-4320-8f22-f2a14284244e https://doi.org/10.1038/cdd.2015.60 |
| Rights: | Springer TDM |
| Dokumentencode: | edsair.doi.dedup.....2e7abf8211bf59636c759be237e7630a |
| Datenbank: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | Cellular necrosis has long been regarded as an incidental and uncontrolled form of cell death. However, a regulated form of cell death termed necroptosis has been identified recently. Necroptosis can be induced by extracellular cytokines, pathogens and several pharmacological compounds, which share the property of triggering the formation of a RIPK3-containing molecular complex supporting cell death. Of interest, most ligands known to induce necroptosis (including notably TNF and FASL) can also promote apoptosis, and the mechanisms regulating the decision of cells to commit to one form of cell death or the other are still poorly defined. We demonstrate herein that intracellular nicotinamide adenine dinucleotide (NAD(+)) has an important role in supporting cell progression to necroptosis. Using a panel of pharmacological and genetic approaches, we show that intracellular NAD(+) promotes necroptosis of the L929 cell line in response to TNF. Use of a pan-sirtuin inhibitor and shRNA-mediated protein knockdown led us to uncover a role for the NAD(+)-dependent family of sirtuins, and in particular for SIRT2 and SIRT5, in the regulation of the necroptotic cell death program. Thus, and in contrast to a generally held view, intracellular NAD(+) does not represent a universal pro-survival factor, but rather acts as a key metabolite regulating the choice of cell demise in response to both intrinsic and extrinsic factors. |
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| ISSN: | 14765403 13509047 |
| DOI: | 10.1038/cdd.2015.60 |