Expression analysis upon NAMPT knockdown in MCF-7 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE13449 | GEO | 2009/05/28
SECONDARY ACCESSION(S): PRJNA113977
REPOSITORIES: GEO
Similar Datasets
Project description:NAMPT is an enzyme in the mammalian NAD+ salvage pathway. Expression microarray analysis was used to study the effect of NAMPT knockdown on gene expression in MCF-7 breast cancer cells. Experiment Overall Design: Stable knockdown of NAMPT was achieved using a retroviral shRNA construct. An shRNA directed against Luciferase was used to generate the Luc control cells. Three independent biological replicates with matching Luc controls were analyzed using Affymetrix U133 A2.0 microarrays.
2009-06-08 | E-GEOD-13449 | biostudies-arrayexpress
Project description:NMNAT1 is a nuclear enzyme in the mammalian NAD+ salvage pathway. Expression microarray analysis was used to study the effect of NMNAT1 knockdown on gene expression in MCF-7 breast cancer cells.
2009-05-28 | GSE13458 | GEO
Project description:Neural stem/progenitor cell (NSPC) proliferation and self-renewal, as well as insult-induced differentiation, decrease markedly with age, but the molecular mechanisms responsible for these declines remain unclear. Here we show that levels of NAD+ and nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in mammalian NAD+ biosynthesis, decrease with age in the hippocampus. Ablation of Nampt in adult NSPCs reduced their pool and proliferation in vivo. The decrease in the NSPC pool during aging can be rescued by enhancing hippocampal NAD+ levels. Nampt is the main source of NSPC NAD+ levels and required for G1/S progression of the NSPC cell cycle. Nampt is also critical for oligodendrocytic lineage fate decisions through a mechanism mediated redundantly by Sirt1 and Sirt2. Ablation of Nampt in the adult NSPCs in vivo reduced NSPC-mediated oligodendrogenesis upon injury. These phenotypes recapitulate defects in NSPCs during aging, implicating Nampt-mediated NAD+ biosynthesis as a mediator of these age-associated functional declines. Total RNA obtained from neurospheres derived from postnatal hippocampi subjected to 48 hours in vitro of incubation with Nampt-specific inhibitor FK866 (10 nM, 4 samples) or vehicle (DMSO, 1:1000, 4 samples).
2014-05-08 | E-GEOD-49784 | biostudies-arrayexpress
Project description:Nicotinamide adenine dinucleotide (NAD+) metabolism becomes dysregulated with age and has emerged as a targetable feature of aging and age-related dysfunction, yet the cellular contexts in which altered NAD+ homeostasis creates therapeutic vulnerabilities remain incompletely defined. Here, we identify senescence as one such context. Senescent cells retained elevated levels of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAM salvage pathway yet exhibited a paradoxical reduction in NAD+ turnover, suggesting a disconnect between protein abundance and enzymatic output. Treatment with SBI-0802162 engaged the spare enzymatic capacity of NAMPT in senescent cells and produced a marked rise in intracellular NAD+ that, when sustained, reinforced their existing stress-associated transcriptional program and selectively reduced senescent cell viability while sparing proliferating cells. Together, these findings identify elevated NAMPT coupled with reduced NAD+ turnover as a metabolic vulnerability in senescent cells and support combined NAMPT activation with dietary NAM as a novel strategy to restore NAD+ homeostasis and improve age-associated inflammation.
2026-09-23 | GSE336534 | GEO
Project description:Nicotinamide adenine dinucleotide (NAD+) metabolism becomes dysregulated with age and has emerged as a targetable feature of aging and age-related dysfunction, yet the cellular contexts in which altered NAD+ homeostasis creates therapeutic vulnerabilities remain incompletely defined. Here, we identify senescence as one such context. Senescent cells retained elevated levels of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAM salvage pathway yet exhibited a paradoxical reduction in NAD+ turnover, suggesting a disconnect between protein abundance and enzymatic output. Treatment with SBI-0802162 engaged the spare enzymatic capacity of NAMPT in senescent cells and produced a marked rise in intracellular NAD+ that, when sustained, reinforced their existing stress-associated transcriptional program and selectively reduced senescent cell viability while sparing proliferating cells. Together, these findings identify elevated NAMPT coupled with reduced NAD+ turnover as a metabolic vulnerability in senescent cells and support combined NAMPT activation with dietary NAM as a novel strategy to restore NAD+ homeostasis and improve age-associated inflammation.
2026-09-23 | GSE336391 | GEO
Project description:Nicotinamide adenine dinucleotide (NAD+) metabolism becomes dysregulated with age and has emerged as a targetable feature of aging and age-related dysfunction, yet the cellular contexts in which altered NAD+ homeostasis creates therapeutic vulnerabilities remain incompletely defined. Here, we identify senescence as one such context. Senescent cells retained elevated levels of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAM salvage pathway yet exhibited a paradoxical reduction in NAD+ turnover, suggesting a disconnect between protein abundance and enzymatic output. In mice, SBI-0802162 reduced circulating nicotinamide (NAM), revealing a limitation of sustained NAM salvage pathway activation and prompting the development of a combination strategy with dietary NAM supplementation. Co-administration of SBI-0802162 and NAM robustly increased tissue NAD+, suppressed select age-associated inflammatory signatures in a tissue-specific manner and preserved physical performance of aged mice. These effects occurred alongside reductions in food intake and body weight, which were observed whether SBI-0802162 and NAM were administered voluntary in the diet or by oral gavage. Together, these findings identify elevated NAMPT coupled with reduced NAD+ turnover as a metabolic vulnerability in senescent cells and support combined NAMPT activation with dietary NAM as a novel strategy to restore NAD+ homeostasis and improve age-associated inflammation.
2026-09-23 | GSE336838 | GEO
Project description:Neural stem/progenitor cell (NSPC) proliferation and self-renewal, as well as insult-induced differentiation, decrease markedly with age, but the molecular mechanisms responsible for these declines remain unclear. Here we show that levels of NAD+ and nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in mammalian NAD+ biosynthesis, decrease with age in the hippocampus. Ablation of Nampt in adult NSPCs reduced their pool and proliferation in vivo. The decrease in the NSPC pool during aging can be rescued by enhancing hippocampal NAD+ levels. Nampt is the main source of NSPC NAD+ levels and required for G1/S progression of the NSPC cell cycle. Nampt is also critical for oligodendrocytic lineage fate decisions through a mechanism mediated redundantly by Sirt1 and Sirt2. Ablation of Nampt in the adult NSPCs in vivo reduced NSPC-mediated oligodendrogenesis upon injury. These phenotypes recapitulate defects in NSPCs during aging, implicating Nampt-mediated NAD+ biosynthesis as a mediator of these age-associated functional declines.
2014-05-08 | GSE49784 | GEO
Project description:As obligate intracellular pathogens, viruses often activate host metabolic enzymes to supply intermediates that support progeny production. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the salvage NAD+ synthesis, is an interferon-inducible protein that inhibits the replication of several RNA and DNA viruses with unknown mechanism. Here we report that NAMPT restricts herpes simplex virus 1 (HSV-1) replication via phosphoribosyl-hydrolase activity toward key viral structural proteins, independent of NAD+ synthesis. Deep mining of enriched phosphopeptides of HSV-1-infected cells identified phosphoribosylated viral structural proteins, particularly glycoproteins and tegument proteins. Indeed, NAMPT dephosphoribosylates viral proteins in vitro and in cells. Chimeric and recombinant HSV-1 carrying phosphoribosylation-resistant mutations show that phosphoribosylation promotes the incorporation of structural proteins into HSV-1 virions and subsequent virus entry. Moreover, loss of NAMPT renders mice highly susceptible to HSV-1 infection. The work describes a hidden enzyme activity of a metabolic enzyme in viral infection and host defense, offering a system to interrogate roles of phosphoribosylation in metazoans.
2024-09-13 | PXD050684 | Pride
Project description:Adoption of Warburg metabolism is critical for macrophage activation in response to lipopolysaccharide (LPS). Macrophages stimulated with LPS (without or with interferon-γ) increase expression of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in NAD+ salvage, and loss of NAMPT activity alters their inflammatory potential. However, events leading to NAD+ salvage-dependence in these cells remain poorly defined. We show that NAD+ depletion and increased NAMPT expression occur rapidly after inflammatory activation and coincide with DNA damage caused by reactive oxygen species (ROS). ROS are produced by Complex III of the mitochondrial electron transport chain, and are required for macrophage activation. We show that DNA damage is associated with PARP activation, which results in NAD+ consumption and in this setting increased NAMPT expression allows the maintenance of NAD+ pools sufficient for GAPDH activity and Warburg metabolism. Our findings provide an integrated explanation for dependency on the NAD+ salvage pathway in inflammatory macrophages.
2019-03-06 | GSE123596 | GEO
Project description:Nuclear factor IB (NFIB) plays an important role in tumors. Our previous study found that NFIB can promote colorectal cancer (CRC) cell proliferation in acidic environments. However, its biological functions and the underlying mechanism in CRC are incompletely understood. Nicotinamide adenine dinucleotide (NAD+) effectively affects cancer cell proliferation. Nevertheless, the regulatory mechanism of NAD+ synthesis in cancer remains to be elucidated. Here we show NFIB promotes CRC proliferation in vitro and growth in vivo, and down-regulation of NFIB can reduce the level of NAD+. In addition, supplementation of NAD+ precursor NMN can recapture cell proliferation in CRC cells with NFIB knockdown. Mechanistically, we identified that NFIB promotes CRC cell proliferation by inhibiting miRNA-182-5p targeting and binding to NAMPT, the NAD+ salvage synthetic rate-limiting enzyme. Our results delineate a combination of high expression of NFIB and NAMPT predicted a clinical poorest prognosis. This work provides potential therapeutic targets for CRC treatment.
2025-06-22 | GSE236756 | GEO