Intracellular NAD levels regulate tumor necrosis factor protein synthesis in a sirtuin-dependent manner
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| Název: | Intracellular NAD levels regulate tumor necrosis factor protein synthesis in a sirtuin-dependent manner |
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| Autoři: | Pierre Paul Prevot, Frederick W. Alt, Oberdan Leo, Frédéric Van Gool, Cyril Gueydan, Antonio Bedalov, Raul Mostoslavsky, Mara Galli, Véronique Kruys, Thibaut De Smedt |
| Zdroj: | Nature Medicine. 15:206-210 |
| Informace o vydavateli: | Springer Science and Business Media LLC, 2009. |
| Rok vydání: | 2009 |
| Témata: | 0301 basic medicine, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, Tumor Necrosis Factor-alpha, Tumor Necrosis Factor-alpha -- biosynthesis, Enzyme-Linked Immunosorbent Assay, Nicotinamide Phosphoribosyltransferase -- metabolism, NAD, Sciences biomédicales, 3. Good health, Mice, 03 medical and health sciences, NAD -- metabolism, Animals, Nicotinamide Phosphoribosyltransferase |
| Popis: | Tumor necrosis factor (TNF) synthesis is known to play a major part in numerous inflammatory disorders, and multiple transcriptional and post-transcriptional regulatory mechanisms have therefore evolved to dampen the production of this key proinflammatory cytokine. The high expression of nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in the nicotinamide-dependent NAD biosynthetic pathway, in cells of the immune system has led us to examine the potential relationship between NAD metabolism and inflammation. We show here that intracellular NAD concentration promotes TNF synthesis by activated immune cells. Using a positive screen, we have identified Sirt6, a member of the sirtuin family, as the NAD-dependent enzyme able to regulate TNF production by acting at a post-transcriptional step. These studies reveal a previously undescribed relationship between metabolism and the inflammatory response and identify Sirt6 and the nicotinamide-dependent NAD biosynthetic pathway as novel candidates for immunointervention in an inflammatory setting. |
| Druh dokumentu: | Article |
| Popis souboru: | 1 full-text file(s): application/pdf; text |
| Jazyk: | English |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm.1906 |
| Přístupová URL adresa: | https://europepmc.org/articles/pmc2845476?pdf=render https://pubmed.ncbi.nlm.nih.gov/19151729 https://pubmed.ncbi.nlm.nih.gov/19151729/ https://www.nature.com/articles/nm.1906 https://www.nature.com/articles/nm.1906.pdf https://europepmc.org/articles/PMC2845476 http://authors.fhcrc.org/397/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845476/ |
| Rights: | Springer TDM CC BY NC ND |
| Přístupové číslo: | edsair.doi.dedup.....6feda68ce9637b82016aa2e17d6c2249 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Tumor necrosis factor (TNF) synthesis is known to play a major part in numerous inflammatory disorders, and multiple transcriptional and post-transcriptional regulatory mechanisms have therefore evolved to dampen the production of this key proinflammatory cytokine. The high expression of nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in the nicotinamide-dependent NAD biosynthetic pathway, in cells of the immune system has led us to examine the potential relationship between NAD metabolism and inflammation. We show here that intracellular NAD concentration promotes TNF synthesis by activated immune cells. Using a positive screen, we have identified Sirt6, a member of the sirtuin family, as the NAD-dependent enzyme able to regulate TNF production by acting at a post-transcriptional step. These studies reveal a previously undescribed relationship between metabolism and the inflammatory response and identify Sirt6 and the nicotinamide-dependent NAD biosynthetic pathway as novel candidates for immunointervention in an inflammatory setting. |
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| ISSN: | 1546170X 10788956 |
| DOI: | 10.1038/nm.1906 |