Effects of nitrate-induced promotion of de novo NAD synthesis in Arabidopsis thaliana
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PROVIDER: PRJNA562646 | ENA |
REPOSITORIES: ENA
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Project description:In higher plants, NAD synthesis starts with the oxidation of aspartate. This oxidation is catalyzed by aspartate oxidase (AO) encoded by a nitrate-inducible gene. To assess the effects of this upregulation of AO gene in response to a nitrate supply, a transgenic line was generated by introduction of AO gene under the control of a mutated AO promoter into the ao knockout mutant. Since, unlike the wild-type AO promoter, this mutated AO promoter was not activated by a nitrate supply, gene expression in this transgenic line was compared with that in another transgenic line that was generated by introduction of AO gene under the regulation of the wild-type AO promoter into the ao knockout mutant. Changes in gene expression in response to a nitrate supply were analyzed in these transgenic lines.
2022-05-18 | GSE136542 | GEO
Project description:Tryptophan metabolism and de novo NAD biosynthesis is associated with behavioural changes in IBD patients. The microbiota and tryptophan de novo syntheses of the distal colon, distal colon and brain of C57BL/6 control mice and Winnie mice littermates with chronic intestinal inflammation were compared using RNA-Seq. Differentially expressed genes were analysed using Micromon software. Changes in tryptophan and nicotinamide metabolism-associated gene expressions, metabolites, and abundance of gut microbiota associated with chronic intestinal inflammation and dysregulated tryptophan metabolism in the Winnie mouse distal colon and brain were apparent. Our findings shed light on the physiological alterations in tryptophan metabolism, specifically its diversion from the serotonergic pathway towards the kynurenine pathway and the consequential effects on de novo NAD+ synthesis, in the context of chronic intestinal inflammation
2024-06-28 | GSE264317 | GEO
Project description:Changes in tryptophan de novo NAD synthesis associated with chronic intestinal inflammation
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Project description:Mycobacteria can synthesize NAD+ using either the de novo biosynthesis pathway or the salvage pathway. The deletion of the three genes involved specifically in the NAD+ de novo biosynthesis pathway in the human pathogen Mycobacterium tuberculosis had no effect on the growth of the strain in vivo. In contrast, the same deletion in the bovine pathogen Mycobacterium bovis resulted in a strain that could not grow in vivo and could only grow in vitro with substantial nicotinamide supplmentation. This striking difference was attributed to the known defect in the nicotinamidase PncA of M. bovis, since introducing the M. tuberculosis pncA gene into the M. bovis strain defective for de novo NAD+ biosynthesis restored growth in vitro and in vivo. This study demonstrates that NAD+ starvation is a cidal event in mycobacteria and confirms that enzymes common to the de novo and salvage pathways may be good drug targets. We also propose that simultaneously targeting both the salvage and the de novo NAD+ biosynthesis pathways represents a potentially effective way to treat infection with tubercle bacilli. To characterize the lethality induced by nicotinamide starvation transcriptional profiling of the auxotrophs was performed. Triplicate 50 mL cultures of M. tuberculosis and M. bovis Delta nadABC mutants were grown in 7H9 OADC glycerol 0.05% tween broth in 500 mL roller bottles to an OD600nm= 0.1 in a roller incubator at 37°C. The cells were washed 1x in PBS and resuspended in 50 mL 7H9 OADC glycerol 0.05% tween broth with or without 20mg/L nicotinamide and returned to the incubator. After 7 days, cultures were harvested. Three biological replicates of each of two species with one dye-flip each
2010-05-14 | E-GEOD-18909 | biostudies-arrayexpress
Project description:Mycobacteria can synthesize NAD+ using either the de novo biosynthesis pathway or the salvage pathway. The deletion of the three genes involved specifically in the NAD+ de novo biosynthesis pathway in the human pathogen Mycobacterium tuberculosis had no effect on the growth of the strain in vivo. In contrast, the same deletion in the bovine pathogen Mycobacterium bovis resulted in a strain that could not grow in vivo and could only grow in vitro with substantial nicotinamide supplmentation. This striking difference was attributed to the known defect in the nicotinamidase PncA of M. bovis, since introducing the M. tuberculosis pncA gene into the M. bovis strain defective for de novo NAD+ biosynthesis restored growth in vitro and in vivo. This study demonstrates that NAD+ starvation is a cidal event in mycobacteria and confirms that enzymes common to the de novo and salvage pathways may be good drug targets. We also propose that simultaneously targeting both the salvage and the de novo NAD+ biosynthesis pathways represents a potentially effective way to treat infection with tubercle bacilli. To characterize the lethality induced by nicotinamide starvation transcriptional profiling of the auxotrophs was performed. Triplicate 50 mL cultures of M. tuberculosis and M. bovis Delta nadABC mutants were grown in 7H9 OADC glycerol 0.05% tween broth in 500 mL roller bottles to an OD600nm= 0.1 in a roller incubator at 37°C. The cells were washed 1x in PBS and resuspended in 50 mL 7H9 OADC glycerol 0.05% tween broth with or without 20mg/L nicotinamide and returned to the incubator. After 7 days, cultures were harvested.
2010-02-24 | GSE18909 | GEO
Project description:Therapeutic strategies to treat acute kidney injury (AKI) are lacking. Preconditioning by hypoxia (HP) and caloric restriction (CR) is highly protective in rodent AKI models. The underlying molecular mechanisms are unknown. A comparative transcriptome analysis after HP and CR identified Kynureninase (KYNU) as a common downstream target. Using a newly generated KYNU-deficient mouse line, we show that KYNU contributes to the protective effect of preconditioning. Metabolome, transcriptome and proteome analyses reveal KYNU as necessary for CR-associated maintenance of nicotinamide adenine dinucleotide (NAD+) levels. Importantly, the impact of CR on the de novo NAD+ biosynthesis pathway can be recapitulated in humans.
2023-02-13 | PXD038328 | Pride
Project description:Recent advances highlight a pivotal role for cellular metabolism in programming immune responses. Here, we demonstrate that cell-autonomous generation of nicotinamide adenine dinucleotide (NAD+) via the kynurenine pathway (KP) regulates macrophage immune function in aging and inflammation. Isotope tracer studies revealed that macrophage NAD+ derives substantially from KP metabolism of tryptophan. Genetic or pharmacological blockade of de novo NAD+ synthesis depleted NAD+, suppressed mitochondrial NAD+-dependent signaling and respiration, and impaired phagocytosis and resolution of inflammation. Innate immune challenge triggered upstream KP activation but paradoxically suppressed cell-autonomous NAD+ synthesis by limiting the conversion of downstream quinolinate to NAD+, a profile recapitulated in aging macrophages. Increasing de novo NAD+ generation in immune-challenged or aged macrophages restored oxidative phosphorylation and homeostatic immune responses. Thus, KP-derived NAD+ operates as a metabolic switch to specify macrophage effector responses. Breakdown of de novo NAD+ synthesis may underlie declining NAD+ levels and rising innate immune dysfunction in aging and age-associated diseases.
| S-EPMC6768398 | biostudies-literature
Project description:Nicotinamide adenine dinucleotide (NAD+) is a co-substrate for several enzymes, including the sirtuin family of NAD+-dependent protein deacylases. Beneficial effects of increased NAD+ levels and sirtuin activation on mitochondrial homeostasis, organismal metabolism and lifespan have been established across species. Here we show that α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), the enzyme that limits spontaneous cyclization of α-amino-β-carboxymuconate-ε-semialdehyde in the de novo NAD+ synthesis pathway, controls cellular NAD+ levels via an evolutionarily conserved mechanism in Caenorhabditis elegans and mouse. Genetic and pharmacological inhibition of ACMSD boosts de novo NAD+ synthesis and sirtuin 1 activity, ultimately enhancing mitochondrial function. We also characterize two potent and selective inhibitors of ACMSD. Because expression of ACMSD is largely restricted to kidney and liver, these inhibitors may have therapeutic potential for protection of these tissues from injury. In summary, we identify ACMSD as a key modulator of cellular NAD+ levels, sirtuin activity and mitochondrial homeostasis in kidney and liver.
| S-EPMC6448761 | biostudies-literature
Project description:Nicotinamide Starvation of Mycobacteria Defective for de novo NAD Biosynthesis
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Project description:FAM120A as a transcriptional co-activator that couples transcription and splicing of lipid synthesis enzymes downstream of mTORC1-SRPK2 signaling. Mechanistically, the mTORC1-activated SRPK2 phosphorylates a splicing factor SRSF1, enhancing its binding to FAM120A. FAM120A directly interacts with a lipogenic transcription factor SREBP1 at active promoters, thereby bridging newly transcribed lipogenic genes to the RNA splicing machinery.
2022-07-02 | GSE207172 | GEO