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| http://purl.uniprot.org/citations/16516847 | http://www.w3.org/2000/01/rdf-schema#comment | "The inflammatory cytokine TNF is known to affect glucose and lipid metabolism, where its action leads to a cachexic state. Despite a well-established connection of TNF to metabolism, the relationship between TNF and NAD(+) metabolism remains unclear. In this report, we evaluated the effects of TNF on NAD(+) metabolism in cells that are TNF's primary autocrine target-macrophages. We designed real-time PCR primers to all NAD(+) metabolic enzymes, which we used to examine TNF-induced changes over time. We found that TNF paradoxically up-regulated enzymes that served to increase NAD(+) levels, such as IDO and PBEF, as well as enzymes that decrease NAD(+) levels, such as CD38 and CD157. The significance of these mRNA changes was evaluated by examining TNF-mediated changes in cellular NAD(+) levels. Treatment of macrophages with TNF decreased NAD(+) levels over time, suggesting that increases in NAD(+)-degrading enzymes were dominant. To evaluate whether this was the case, we measured TNF-mediated changes in NAD(+) levels in animals where CD38 was genetically deleted. In CD38-/-macrophages, the effects of TNF were reversed, with TNF increasing NAD(+) levels over time. The significance of our findings is threefold: (1) we establish that TNF affects NAD(+) metabolism by regulating the expression of major NAD(+) metabolic enzymes, (2) TNF-induced decreases in cellular NAD(+) levels were carried out through the up-regulation of extracellularly situated enzymes, and (3) we provide a mechanism for the observed clinical connection of TNF-dependent diseases to tissue reductions in NAD(+) content."xsd:string |
| http://purl.uniprot.org/citations/16516847 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.bbrc.2006.02.109"xsd:string |
| http://purl.uniprot.org/citations/16516847 | http://purl.uniprot.org/core/author | "Iqbal J."xsd:string |
| http://purl.uniprot.org/citations/16516847 | http://purl.uniprot.org/core/author | "Zaidi M."xsd:string |
| http://purl.uniprot.org/citations/16516847 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16516847 | http://purl.uniprot.org/core/name | "Biochem Biophys Res Commun"xsd:string |
| http://purl.uniprot.org/citations/16516847 | http://purl.uniprot.org/core/pages | "1312-1318"xsd:string |
| http://purl.uniprot.org/citations/16516847 | http://purl.uniprot.org/core/title | "TNF regulates cellular NAD+ metabolism in primary macrophages."xsd:string |
| http://purl.uniprot.org/citations/16516847 | http://purl.uniprot.org/core/volume | "342"xsd:string |
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