Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Systemic metabolite changes due to Hypoxia

ABSTRACT: Prolonged cellular hypoxia leads to energetic failure and death. However, sublethal hypoxia can trigger an adaptive response called hypoxic preconditioning. While prolyl-hydroxylase (PHD) enzymes and hypoxia inducible factors (HIFs) have been identified as key elements of oxygen sensing machinery, the mechanisms by which hypoxic preconditioning protects against insults remain unclear. Here, we perform serum metabolomic profiling to assess alterations induced by hypoxic preconditioning. We discover that hypoxic preconditioning increases serum kynurenine levels and enhance kynurenine biotransformation leading to preservation of NAD+ in the post-ischemic kidney. Furthermore, we show that Indoleamine 2,3-dioxygenase 1 (Ido1) deficiency abolishes the systemic increase of kynurenine and the subsequent renoprotection generated by hypoxic preconditioning. Importantly, exogenous administration of kynurenine restores the hypoxic preconditioning in the context of Ido1 deficiency. Collectively, our findings demonstrate a critical role of Ido1/kynurenine axis in mediating hypoxic preconditioning

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Blood

SUBMITTER: Pinelopi Kapitsinou

PROVIDER: ST001865 | MetabolomicsWorkbench | Thu Jul 01 00:00:00 BST 2021

REPOSITORIES: MetabolomicsWorkbench

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	mwtab	Other

Items per page:

1 - 1 of 1

Similar Datasets

Systemic metabolite changes due to PHD inhibition

Project description:Prolonged cellular hypoxia leads to energetic failure and death. However, sublethal hypoxia can trigger an adaptive response called hypoxic preconditioning. While prolyl-hydroxylase (PHD) enzymes and hypoxia inducible factors (HIFs) have been identified as key elements of oxygen sensing machinery, the mechanisms by which hypoxic preconditioning protects against insults remain unclear. Here, we perform serum metabolomic profiling to assess alterations induced by hypoxic preconditioning. We discover that hypoxic preconditioning increases serum kynurenine levels and enhance kynurenine biotransformation leading to preservation of NAD+ in the post-ischemic kidney. Furthermore, we show that Indoleamine 2,3-dioxygenase 1 (Ido1) deficiency abolishes the systemic increase of kynurenine and the subsequent renoprotection generated by hypoxic preconditioning. Importantly, exogenous administration of kynurenine restores the hypoxic preconditioning in the context of Ido1 deficiency. Collectively, our findings demonstrate a critical role of Ido1/kynurenine axis in mediating hypoxic preconditioning

2021-07-03 | ST001866 | MetabolomicsWorkbench

Hypoxia-sensing by Colitogenic CD4+ T cells Is Regulated by the Histone Demethylase UTX [H3K27me3 CUT&Tag]

Project description:Hypoxia exacerbates tissue damage in inflammatory bowel disease (IBD). To counteract the deleterious effects of oxygen deprivation, cells within hypoxic tissues activate multiple adaptive mechanisms. Much attention has focused on adaptive pathways regulated by HIF (hypoxia inducible factor) transcription factors, and pharmacologic HIF stabilization is a promising therapeutic approach for IBD. However, recent evidence suggests that hypoxia-induction of cellular transcriptional programs can be mediated not only by HIF transcription factors, but also by oxygen-sensing epigenetic regulator, UTX. Here, we identify a key role for an UTX in modulating colitis severity. Unlike HIF-mediated pathways that act on gut epithelial cells, UTX-mediated pathways function in a T cell-intrinsic manner to protect against colitis. Hypoxia impairs the histone demethylase activity of UTX, which leads to accumulation of repressive H3K27me3 marks at IL12/STAT4 pathway genes (Il12rb2, Tbx21, and Ifng), decreased CD4+ T cell IFN-γ production, and increased CD4+ regulatory T cells (Tregs). Moreover, T cell specific UTX deletion protects mice from autoimmune colitis, which demonstrates that deactivation of UTX restores immune regulation in hypoxia-associated inflammation. Together these findings suggest that modulating UTX’s histone demethylase activity in T cells may be a new pharmacologic target for harnessing hypoxia-induced adaptive pathways in colitis.

2023-12-01 | GSE236300 | GEO

Hypoxia-sensing by Colitogenic CD4+ T cells Is Regulated by the Histone Demethylase UTX [RNA-seq]

2023-12-01 | GSE236299 | GEO

Expression variation between VHLR200w homozygous verse wildtype control

2014-04-23 | GSE40227 | GEO

Expression variation between VHLR200w homozygous verse wildtype control

Project description:Hypoxia may cause pulmonary and brain edema, pulmonary hypertension, aberrant metabolism and early mortality. To better understand pathological processes associated with hypoxia, we examined gene expression in Chuvash polycythemia (CP) blood mononuclear cells. CP is a congenital disorder of up-regulated hypoxic response at normoxia wherein VHLR200W homozygosity leads to elevated hypoxia inducible factor (HIF)-1 and HIF-2 levels, thromboses, pulmonary hypertension, lower systemic blood pressure (SBP) and increased mortality. VHLR200W homozygotes are often treated by phlebotomy resulting in iron deficiency, allowing us to evaluate an interaction of augmented hypoxia sensing with iron deficiency. Expression was profiled for 8 VHLR200W homozygotes (CP21, CP23, CP26_2, CP37, CP40, CP43, CP45, CP46) and 17 VHL wildtype individuals (CP48, CP49, CP50, CP51, CP52, CP53, CP55, CP57, CP58, CP59, CP61, CP62, CP63, CP65, CP66, CP67_2, CP68), matched for normal iron status as reflected in serum ferritin concentration. Additional studies including 16 VHLR200W homozygotes with low ferritin (CP22, CP24, CP25, CP28, CP29, CP30, CP31, CP32, CP34, CP35, CP36, CP39, CP41, CP42, CP44, CP47) indicated that iron deficiency generally affects the induction effect of VHLR200W. Two wildtype individuals (CP54, CP56) had no serum ferritin concentration record and two wildtype individuals (CP60, CP64) were defined as iron deficiency subject, which were not included in further expression analysis.

2014-04-23 | E-GEOD-40227 | biostudies-arrayexpress

Comparison of proteomic responses to individual and combinatorial copper and iron deficiencies in Arabidopsis thaliana rosettes.

Project description:Purpose: plants exposed to multiple simultaneous adverse growth conditions trigger molecular responses that differ from the sum of those to individual stressors. Copper and iron are fundamental elements required for proper photosynthesis, energy production, DNA metabolism and hormone sensing, among all. Therefore, copper and iron deprivation limits plant yield. In natural environments, simultaneous deficiency to copper and iron can occur. As part of a multiple high-throughput study to identify combinatorial responses to both copper and iron deficiency, proteomic profiling of Arabidopsis thaliana rosette leaves exposed to copper and/or iron deficiencies have been conducted.

2020-06-22 | PXD013598 | Pride

High oxygen prevents fetal lethality due to lack of catecholamines

Project description:The catecholamine norepinephrine is required for fetal survival, but its essential function is unknown. When catecholamine-deficient [tyrosine hydroxylase (Th) null] mouse fetuses die at E13.5-E14.5, they resemble wild type fetuses exposed to hypoxia. They exhibit bradycardia (28% reduction in heart rate), thin ventricular myocardium (20% reduction in tissue), epicardial detachment, and death with vascular congestion, hemorrhage and edema. At E12.5, prior to the appearance of morphological deficits associated with Th deletion, catecholamine-deficient fetuses are preferentially killed by experimentally-induced hypoxia and have lower tissue pO2 than wild type siblings. Catecholamine-deficient fetuses also induced HIF-1 target genes to a greater extent than wild type siblings, supporting the notion that null fetuses experience greater hypoxia or have an enhanced response to hypoxia. Hypoxia induces a 13-fold increase in plasma norepinephrine levels, which would be expected to increase heart rate, thereby, improving oxygen delivery in wild type mice. Surprisingly, increasing maternal oxygen (FiO2 33% or 63%) prevents the effects of catecholamine-deficiency, restoring heart rate, myocardial mass and survival of Th null fetuses. We suggest that norepinephrine mediates fetal survival by maintaining oxygen homeostasis as vulnerability to constitutive hypoxia increases as fetal growth accelerates during normal development. Keywords: Comparative with respect to genotype and oxygen conditions The first aim was to compare gene expression of E12.5 mouse fetuses between wild type (Th+/+) versus tyrosine hydroxylase null (Th-/-) animals from normoxic dams. This resulted in 6 arrays. The second aim compared wild type and tyrosine hydroxylase null E12.5 fetuses from dam exposed to hypoxia (8% oxygen) for 6 hours prior to sacrifice at E12.5 of gestation. This resulted in 6 arrays. The third aim was to compare HIF-1 targets behind wt and null fetuses

2008-06-03 | E-GEOD-10341 | biostudies-arrayexpress

Mitochondria preconditioning delays aging and associated diseases in C. elegans impacting on key ferroptosis players

Project description:Excessive iron accumulation or deficiency have detrimental consequences across species, leading to a variety of pathologies in humans. In the nematode Caenorhabditis elegans severe iron as well as oxygen deprivation induce developmental arrest. Instead, hypoxia preconditioning protects against severe hypoxia-induced neuromuscular damage and sub-lethal levels of iron depletion extend lifespan in C. elegans. The positive health outcomes of applying hypoxia preconditioning are obvious but have low feasible application. Here, we thus assessed the potential beneficial effects of genetic and chemical interventions acting via mild iron instead of oxygen depletion. We show that limiting iron availability through frataxin silencing or the iron chelator bipyridine, similar to hypoxia preconditioning, protect against hypoxia-, age- and proteotoxicityinduced neuromuscular deficits. Mechanistically, our data suggest that the beneficial effects elicited by frataxin silencing are at least in part mediated by counteracting ferroptosis, a form of non-apoptotic cell death specifically mediated by iron-induced lipid peroxidation. These is achieved by impacting on different key players of the ferroptosis machinery and likely via novel, gpx-independent redox systems. We thus point to ferroptosis inhibition as a novel strategy to promote healthy aging.

2023-04-17 | PXD040724 | Pride

High oxygen prevents fetal lethality due to lack of catecholamines

2008-06-03 | GSE10341 | GEO

Loss of phospholipase PLAAT3 causes a mixed lipodystrophic and neurological syndrome due to impaired PPAR? signaling

Project description:PLAAT3 is a phospholipid modifying enzyme predominantly expressed in neural and white adipose tissue (WAT). It is a potential drug target for metabolic syndrome as Plaat3 deficiency in mice protects against diet-induced obesity. We identified seven patients from four unrelated consanguineous families, with homozygous loss-of-function variants in PLAAT3, presenting a severe lipodystrophy syndrome (LS) associated with metabolic complications, as well as neurological features including demyelinating neuropathy and intellectual disability. Multi-omics analysis of mouse Plaat3-/- and patient-derived WAT showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in the signaling of PPAR?, the master regulator of adipocyte differentiation. The present dataset describes the proteomics shotgun analysis of WAT samples from Plaat3-/- and Plaat3-/+ mice. We found that proteins involved in fatty acid metabolic and lipid biosynthetic processes were less abundant in Plaat3-/- WAT, whereas proteins involved in autophagy and catabolism were more abundant. In line with transcriptomics data obtained from mice and human WAT, PPAR? and its coactivators were identified as strong transcriptional regulators within the set of downregulated proteins. Along with validation experiments in PLAAT3-deficient human adipose stem cells, these findings establish PLAAT3 deficiency as a novel hereditary LS with neurological manifestations, caused by a PPAR?-dependent defect in WAT differentiation and function.

2023-08-29 | PXD038815 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data