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Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide

ABSTRACT: Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide

PROVIDER: PRJNA1111813 | ENA |

REPOSITORIES: ENA

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Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide

Project description:Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide

| PRJNA1111814 | ENA

Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide

Project description:During an immune response, macrophages specifically reprogramme their metabolism to support functional changes. Here, we revealed that nucleotide metabolism is one of the most significantly reprogrammed pathways upon classical activation. Specifically, de novo synthesis of pyrimidines is maintained up to uridine monophosphate, but blocked at cytidine triphosphate and deoxythymidine monophosphate synthesis; de novo synthesis of purines is shut off at the last step (catalysed by AICAR transformylase/IMP cyclohydrolase), and cells switch to increased purine salvage. Nucleotide degradation to nitrogenous bases is upregulated but complete oxidation of purine bases (catalysed by xanthine oxidoreductase) is inhibited, diverting flux into salvage. Mechanistically, nitric oxide was identified as a major regulator of nucleotide metabolism, simultaneously driving multiple key changes, including the transcriptional downregulation of Tyms and profound inhibition of AICAR transformylase/IMP cyclohydrolase and XOR. Inhibiting purine salvage using HGPRT knockout or inhibition alters the expression of many stimulation-induced genes, suppresses macrophage migration and phagocytosis, and increases the proliferation of the intracellular parasite Toxoplasma gondii. Together, these results thoroughly uncover the dynamic reprogramming of macrophage nucleotide metabolism upon classical activation and elucidate the regulatory mechanisms and functional significance of such reprogramming.

2025-07-16 | GSE267546 | GEO

Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide

2025-07-16 | GSE267544 | GEO

Nitric oxide modulates metabolic remodelling and immunometabolism in inflammatory murine macrophages

Project description:Classical stimulation of macrophages (MLPS/IFNγ) elicits the expression of inducible nitric oxide synthase (iNOS), generating large amounts of nitric oxide (NO) and inhibiting respiration. Consequent upregulation of glycolysis and a disrupted tricarboxylic acid (TCA) cycle underpin this switch to a pro-inflammatory phenotype. Here we show that the NOS cofactor tetrahydrobiopterin (BH4) modulates key aspects of metabolic remodelling in activated bone-marrow-derived macrophages (BMDMs) via NO production. Using two complementary mouse models that each lack the capacity for inducible NO generation, through different mechanisms, we reveal that NO regulates macrophage respiratory function via changes in the abundance of critical N-module subunits in Complex I, by HIF1α-mediated glycolytic remodelling, and by modulating levels of the critical TCA cycle metabolites, and inflammatory mediators, citrate, succinate, and itaconate. Taken together, our findings reveal new critical roles for iNOS-derived NO that are required for metabolic remodelling and cytokine production in macrophage inflammatory responses.

2019-05-31 | PXD010628 | Pride

Role of nitric oxide and nitric oxide synthase isoforms in pulmonary emphysema.

Project description:The purpose of this study is to comprehensively elucidate the role of nitric oxide and nitric oxide synthase isoforms in pulmonary emphysema using cap analysis of gene expression (CAGE) sequencing.

2021-01-18 | GSE164521 | GEO

Oleic acid-dependent modulation of Nitric Oxide Associated 1 protein levels regulate nitric oxide mediate signaling in plant defense.

2012-08-01 | GSE36797 | GEO

Role of nitric oxide and nitric oxide synthase isoforms in pulmonary emphysema.

Project description:Role of nitric oxide and nitric oxide synthase isoforms in pulmonary emphysema.

| PRJNA691047 | ENA

Oleic acid-dependent modulation of Nitric Oxide Associated 1 protein levels regulate nitric oxide mediate signaling in plant defense.

Project description:Oleic acid-dependent modulation of Nitric Oxide Associated 1 protein levels regulate nitric oxide- mediate signaling in plant defense. Nitric Oxide, Oleic acid, Salicylic acid, Arabidopsis, Defense Wild-type Col-0, mutant genotypes ssi2, ssi2 act1 and ssi2 sid2 with three biological replicates were analyzed (one array each)

2012-07-31 | E-GEOD-36797 | biostudies-arrayexpress

Transcriptome response to nitric oxide in Pseudomonas aeruginosa

2014-12-08 | GSE58862 | GEO

Transcriptome response to nitric oxide in Pseudomonas aeruginosa

Project description:DNA microarray analysis was employed to investigate the transcriptome response to nitric oxide in Pseudomonas aeruginosa. We focused on the role played by the nitric oxide-response regulators DNR and FhpR and an oxygen-response regulator ANR in the response. The transcriptome profiles of the P. aeruginosa strains before and after exposure to nitric oxide under the microaerobic conditions were analyzed. Wild type, its anr, dnr, and fhpR mutants, and the anr mutant that express dnr were used for the analyses. Pseudomonas aeruginosa wild type (PAO1ut), anr mutant (RManr), dnr mutant (RMdnr), anr mutant that constitutively expresses DNR (RManrEXdnr), and fhpR mutant (PDM2665) were cultivated microaerobically in LB in 1-liter jar fermenter. When optical density at 600 nm reached 0.3, nitric oxide-saturated water was added to the medium (final nitric oxide concentration was 20 micro-M). RNA was isolated from a 10 ml aliquot of the culture prior to the addition of nitric oxide and at 5 min after the addition. The experiment was performed in duplicate independent cultures.

2014-12-08 | E-GEOD-58862 | biostudies-arrayexpress

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