Noxa regulation of malate aspartate shuttle
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): T-cells
DISEASE(S): Cancer
PROVIDER: ST000146 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:Asthma is a complex syndrome associated with episodic decompensations provoked by aeroaller-gen exposures. The underlying pathophysiological states driving exacerbations are latent in the resting state and do not adequately inform biomarker-driven therapy. A better understanding of the pathophysiological pathways driving allergic exacerbations is needed. We hypothesized that disease-associated pathways could be identified in humans by unbiased metabolomics of bron-choalveolar fluid (BALF) during the peak inflammatory response provoked by a bronchial aller-gen challenge. We analyzed BALF metabolites in samples from 12 volunteers who underwent segmental bronchial antigen provocation (SBP-Ag). Metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS) followed by pathway analysis and cor-relation with airway inflammation. SBP-Ag induced statistically significant changes in 549 fea-tures that mapped to 72 uniquely identified metabolites. From these features, two distinct induci-ble metabolic phenotypes were identified by the principal component analysis, partitioning around medoids (PAM) and k-means clustering. Ten index metabolites were identified that in-formed the presence of asthma-relevant pathways, including unsaturated fatty acid produc-tion/metabolism, mitochondrial beta oxidation of unsaturated fatty acid, and bile acid metabolism. Pathways were validated using proteomics in eosinophils. A segmental bronchial allergen chal-lenge induces distinct metabolic responses in humans, providing insight into pathogenic and pro-tective endotypes in allergic asthma.
2022-06-09 | PXD033172 | Pride
Project description:Teneurin C-terminal associated peptide (TCAP) is an ancient bioactive peptide that is highly conserved in metazoans. TCAP administration reduces cellular and behavioural stress in vertebrate and urochordate models, yet despite numerous studies in higher animals, there is limited knowledge of its role in invertebrates. In particular, there are no studies on TCAP’s effects on the heart of any metazoan, which is a critical organ in the stress response. We used the Sydney rock oyster (SRO) as an invertebrate model to investigate a potential role for sroTCAP in regulating cardiac activity, including during stress. sroTCAP is localized to the neural innervation network of the SRO heart, and demonstrated binding with various heart proteins related to metabolism and stress, including SOD, GAPDH and metabotropic glutamate receptor. Intramuscular injection of sroTCAP (10 pmol) significantly altered the expression of heart genes that are known to regulate remodelling processes under different conditions, and modulated several gene families responsible for stress mitigation. sroTCAP (1 and 10 pmol) was shown to cause transient bradycardia (heart rate was reduced by up to 63% and for up to 40 min post-administration), indicative of an unstressed state. In summary, this study has established a role for a TCAP in the regulation of cardiac activity through modulation of physiological and molecular components associated with energy conservation, stress and adaptation. This represents a novel function for TCAP and may have implications for higher-order metazoans.
2023-01-27 | PXD039155 | Pride
Project description:A growing body of evidence supports the importance of T cell responses to protect against severe influenza, promote viral clearance and ensure long-term immunity. Plant-derived virus-like particle (VLP) vaccines bearing influenza hemagglutinin (HA) have been shown to elicit strong humoral and CD4+ T cell responses in both pre-clinical and clinical studies. To better understand the immunogenicity of theses vaccines, we tracked the intracellular fate of a model HA (A/California/07/2009 H1N1) in human monocyte-derived macrophages (MDMs) following delivery either as VLPs (H1-VLP) or in soluble form. High-resolution tandem mass spectrometry identified 131 HA-derived peptides associated with MHC I in the H1-VLP-treated MDMs. Together with immunostaining and microscopy results, these data suggest that HA delivery to antigen-presenting cells on plant-derived VLPs facilitates antigen uptake, endosomal processing and cross-presentation. These observations may help explain the broad and cross-reactive immune responses generated by these vaccines.
2019-05-28 | PXD010519 | Pride
Project description:The human flavoenzyme D-aspartate oxidase (hDASPO) controls the level of D-aspartate in the brain, a molecule acting as an agonist of NMDA receptors and modulator of AMPA and mGlu5 receptors. hDASPO-induced D-aspartate degradation prevents age-dependent deterioration of brain functions and is related to psychiatric disorders such as schizophrenia and autism. Notwithstanding this crucial role, less is known about hDASPO regulation. Here, we report that hDASPO is nitrosylated in vitro, while no evidence of sulfhydration and phosphorylation is apparent: nitrosylation affects the activity of the human flavoenzyme to a limited extent. Furthermore, hDASPO interacts with the primate-specific protein pLG72 (a well-known negative chaperone of D-amino acid oxidase, the enzyme deputed to D-serine degradation in the human brain), yielding a ~114 kDa complex, with a micromolar dissociation constant, promoting the flavoenzyme inactivation. At the cellular level, pLG72 and hDASPO generate a cytosolic complex: the expression of pLG72 negatively affects the hDASPO level by reducing its half-life. We propose that pLG72 binding may represent a protective mechanism aimed at avoiding cytotoxicity due to H2 O2 produced by the hDASPO enzymatic degradation of D-aspartate, especially before the final targeting to peroxisomes.
| S-EPMC10588558 | biostudies-literature
Project description:The enzyme aspartate transcarbamoylase (ATCase, EC 2.1.3.2 of Escherichia coli), which catalyzes the committed step of pyrimidine biosynthesis, is allosterically regulated by all four ribonucleoside triphosphates (NTPs) in a nonlinear manner. Here, we dissect this regulation using the recently developed approach of random sampling-high-dimensional model representation (RS-HDMR). ATCase activity was measured in vitro at 300 random NTP concentration combinations, each involving (consistent with in vivo conditions) all four NTPs being present. These data were then used to derive a RS-HDMR model of ATCase activity over the full four-dimensional NTP space. The model accounted for 90% of the variance in the experimental data. Its main elements were positive ATCase regulation by ATP and negative by CTP, with the negative effects of CTP dominating the positive ones of ATP when both regulators were abundant (i.e., a negative cooperative effect of ATP x CTP). Strong sensitivity to both ATP and CTP concentrations occurred in their physiological concentration ranges. UTP had only a slight effect, and GTP had almost none. These findings support a predominant role of CTP and ATP in ATCase regulation. The general approach provides a new paradigm for dissecting multifactorial regulation of biological molecules and processes.
| S-EPMC2732338 | biostudies-literature
Project description:MicroRNAs are important negative regulators of protein coding gene expression, and have been studied intensively over the last few years. To this purpose, different measurement platforms to determine their RNA abundance levels in biological samples have been developed. In this study, we have systematically compared 12 commercially available microRNA expression platforms by measuring an identical set of 20 standardized positive and negative control samples, including human universal reference RNA, human brain RNA and titrations thereof, human serum samples, and synthetic spikes from homologous microRNA family members. We developed novel quality metrics in order to objectively assess platform performance of very different technologies such as small RNA sequencing, RT-qPCR and (microarray) hybridization. We assessed reproducibility, sensitivity, quantitative performance, and specificity. The results indicate that each method has its strengths and weaknesses, which helps guiding informed selection of a quantitative microRNA gene expression platform in function of particular study goals.
2013-09-01 | E-MTAB-1815 | biostudies-arrayexpress
Project description:In this study, primary human monocyte-derived macrophages were exposed to plant-derived virus-like particles (VLPs) bearing influenza A hemagglutinin (HA) or soluble influenza HA, as control. Immunopurified MHC class I-associated peptides were analysed by nano-flow high pressure liquid chromatography coupled to high-resolution dopant-assisted electrospray ionisation mass spectrometry. A total of 109 host-derived MHC I peptides were identified in the VLP-treated samples, two of which were also detected in controls. The peptides unique to VLP treatment were, on average, ~13 amino acid residues long, more basic and hydrophilic, and were mainly processed via proteolysis by matrix metalloproteinases and cathepsins. The proteins associated with these peptides were primarily involved in cellular, metabolic and regulatory processes and activated several pathways including inflammation stimulation and attenuation, response to stimuli, innate and adaptive immunity, clathrin-mediated endocytosis, protein synthesis and endo-lysosomal degradation. This study is the first report to describe the response of a primary human antigen-presenting cell to nanoparticulate vs. soluble antigen exposure from an immunopeptidomics point of view.
2022-02-24 | PXD010741 | Pride
Project description:In order to determine whether dis-regulation of a genetic pathway could explain the increased apoptosis of parp-2-/- double positive thymocytes, the gene expression profiles in double positive thymocytes derived from wild-type and parp-2-/- mice were analysed using Affymetrix oligonucleotide chips (mouse genome 430 2.0).
2007-05-23 | E-MEXP-755 | biostudies-arrayexpress
Project description:BackgroundGenetic studies have implicated disrupted-in-schizophrenia-1 (DISC1) as a risk factor for a wide range of mental conditions, including schizophrenia. Because N-methyl-D-aspartate receptor (NMDAR) dysfunction has been strongly linked to the pathophysiology of these conditions, we examined whether the NMDAR is a potential target of DISC1.MethodsDISC1 was knocked down with a small inference RNA. NMDAR-mediated currents were recorded and NMDAR expression was measured.ResultsWe found that cellular knockdown of DISC1 significantly increased NMDAR currents in cortical cultures, which were accompanied by an increase in the expression of NMDAR subunit, GluN2A. NMDAR-mediated synaptic response in prefrontal cortical pyramidal neurons was also increased by DISC1 knockdown in vivo. The effect of DISC1 knockdown on NMDAR currents in cortical cultures was blocked by protein kinase A (PKA) inhibitor, occluded by PKA activator, and prevented by phosphodiesterase 4 inhibitor. Knockdown of DISC1 caused a significant increase of cyclic adenosine monophosphate response element-binding protein (CREB) activity. Inhibiting CREB prevented the DISC1 deficiency-induced increase of NMDAR currents and GluN2A clusters.ConclusionsOur results suggest that DISC1 exerts an important impact on NMDAR expression and function through a phosphodiesterase 4/PKA/CREB-dependent mechanism, which provides a potential molecular basis for the role of DISC1 in influencing NMDAR-dependent cognitive and emotional processes.
| S-EPMC3864617 | biostudies-literature
Project description:rs13_01_lao - down/up regulation of nad biosynthesis in arabidopsis and role of l-aspartate oxidase - Study of the biosynthesis of NAD in Arabidopsis. Involvment of L-Aspartate oxidase gene using T-DNA mutant (SAIL1145_B10) and overexpressor lines (promotor 35S, vector PCW162) at the same developmental stage (12 leaves) - Study of the biosynthesis of NAD in Arabidopsis. Involvment of L-Aspartate oxidase gene using T-DNA mutant (SAIL1145_B10) and overexpressor lines (promotor 35S, vector PCW162) at the same developmental stage (12 leaves)
2018-10-01 | GSE120564 | GEO