Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The thioredoxin-1 system is essential for fueling DNA synthesis during T cell metabolic reprogramming and proliferation

ABSTRACT: The thioredoxin-1 system is essential for fueling DNA synthesis during T cell metabolic reprogramming and proliferation

PROVIDER: PRJNA418977 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

The thioredoxin-1 system is essential for fueling DNA synthesis during T cell metabolic reprogramming and proliferation

Project description:The thioredoxin-1 (Trx1) system is a key player of the cellular redox balance and a sensor of energy and glucose metabolism. Here we report critical c-Myc-dependent activation of the Trx1 system during glucose-driven T cell expansion during development and immune responses but endogenous Trx1-repression during quiescence. Thioredoxin-reductase-1 (Txnrd1)-deletion in CD4-CD8- thymocytes prevented their expansion, while deletion in CD4+CD8+ thymocytes did not affect further maturation and peripheral homeostasis of T-cells. Moreover, B cell development was Txnrd1-independent. Txnrd1 was critical for expansion of activated T cells. Unbiased metabolomics revealed that Txnrd1 is necessary for donating reducing equivalent to ribonucleotide reductase (RNR) at the last step of nucleotide biosynthesis. Impaired availability of 2’-deoxyribonucleotides induced the DNA damage response and cell cycle arrest of Txnrd1-deficient T cells. These results uncover a pivotal role of the Trx1 system in metabolic reprograming of thymic and peripheral T cells and provide a rationale for targeting of Txnrd1 in T-cell leukemia.

2018-03-15 | GSE107090 | GEO

The thioredoxin-1 system is essential for fueling DNA synthesis during T-cell metabolic reprogramming and proliferation.

Project description: Not available

| S-EPMC5945637 | biostudies-literature

Shifted Metabolic Bias in Livers of Mice Lacking Hepatocytic Thioredoxin Reductase-1 Protects Against Acetaminophen Toxicity

2013-06-08 | GSE37874 | GEO

Shifted Metabolic Bias in Livers of Mice Lacking Hepatocytic Thioredoxin Reductase-1 Protects Against Acetaminophen Toxicity

Project description:Genetic disruption of thioredoxin reductase 1 protects against acetaminophen (APAP) toxicity. To determine the role of the thioredoxin system on xenobiotic metabolism we challeneged wildtype and txnrd1liver-null mice with acetaminophen. Adult male wildtype and txnrd1 liver-null mice (C57BL6/J) were treated with either saline (PBS) or 100mg/kg APAP. Liver RNA was harvested eight hours after challenge and processed for microarray analysis. Comparison of 2 treatment conditions in 2 genotypes, biological replicates in triplicate.

2013-06-08 | E-GEOD-37874 | biostudies-arrayexpress

Functions and adaptive responses to oxidative stress of the thioredoxin and glutathione pathways in Clostridium acetobutylicum

Project description:Oxidative stress is harmful for organism and occurs when the cells exposed to superoxid, hydrogen peroxide and alkylhydroperoxides. In microorganism, the glutathione- and thioredoxin-dependent reduction systems are universal and play an important role in response to defending oxidative stress. The _-glutamylcysteine synthetase (_-GCS) is an essential enzyme to biosynthesize the tripeptide glutathione (GSH) in organism. Similarly, thioredoxin reductase is an important enzyme in thioredoxin-dependent reduction system. In Clostridium acetobutylicum, the _-glutamylcysteine synthetase (encoded by CAC1539, gcs) and thioredoxin reductase (encoded by CAC1548, trxB) were inactivated using ClosTron technology. The gcs mutant grew insufficiently and consumed less glucose in the phosphate-limited continuous culture and exhibited more sensitive to oxidative stress. The trxB mutant just exhibited lower growth rate and less glucose uptake in the solventogenic phase, compared to wild type. The DNA microarrays were performed to investigate the transcripome difference between wild type and the mutants. In gcs mutant, the genes related to chemotaxis and flagella biosynthesis proteins were induced significantly and in the trxB mutant, the sporulation genes were induced largely. Based on the phenotypes and transcriptome comparison results, the relationship between GSH- and Trx-dependent induction systems was discussed in Clostridium acetobutylicum.

2015-04-13 | E-MTAB-2747 | biostudies-arrayexpress

Epigenetic changes of the thioredoxin system in the tx-j mouse model and in patients with Wilson disease

Project description:Wilson disease (WD) is caused by mutations in the copper transporter ATP7B, leading to copper accumulation in the liver and brain. Excess copper inhibits S-adenosyl-L-homocysteine hydrolase, leading to variable WD phenotypes from widespread alterations in DNA methylation and gene expression. Previously, we demonstrated that maternal choline supplementation in the Jackson toxic milk (tx-j) mouse model of WD corrected higher thioredoxin 1 transcript levels in fetal liver. Here, we investigated the effect of maternal choline supplementation on genome-wide DNA methylation patterns in tx-j fetal liver by whole-genome bisulfite sequencing (WGBS). Tx-j Atp7b genotype-dependent differences in DNA methylation were corrected by choline for genes including, but not exclusive to, oxidative stress pathways. To examine phenotypic effects of postnatal choline supplementation, tx-j mice were randomized to one of six treatment groups: with or without maternal and/or continued choline supplementation, and with or without copper chelation with penicillamine (PCA) treatment. Hepatic transcript levels of thioredoxin 1 and peroxiredoxin 1 were significantly higher in mice receiving maternal and continued choline with or without PCA treatment compared to untreated mice. A comparison of WGBS of human WD liver compared to tx-j mouse liver demonstrated a significant overlap of differentially-methylated genes associated with ATP7B deficiency. Further, eight genes in the thioredoxin pathway were differentially methylated in human WD liver samples. In summary, Atp7b deficiency and choline supplementation have a genome-wide impact, including on thioredoxin system-related genes, in tx-j mice. These findings could explain the variability of WD phenotype and suggest new complementary treatment options for WD.

2018-07-25 | GSE117592 | GEO

MEAF6 is essential for proliferation and plays a role in the assembly of KAT7 complexes

Project description:MEAF6 is essential for proliferation and plays a role in the assembly of KAT7 complexes.

2020-09-23 | PXD020422 | JPOST Repository

Thioredoxin-1 Alters Anti-Tumor T Cell Immuno-Metabolic Phenotype

Project description:ABSTRACT Adoptive transfer of tumor epitope reactive T cells is a promising strategy to control tumor growth. However, chronically stimulated T cells expanded for adoptive cell transfer (ACT) are susceptible to cells death in an oxidative tumor microenvironment. Since oxidation of cell surface thiols (c-SH) also alters functionality of proteins, we hypothesized that increased level of thioredoxin, an anti-oxidant molecule that facilitates reduction of proteins by cysteine thioldisulfide exchange, in T cells will result in sustained anti-tumor function. Using Pmel-Trx1 transgenic mouse derived splenic T cells we observed higher c-SH expression that inversely correlated with ROS, and susceptibility to TCR restimulation or oxidation mediated cell death. These Trx1 overexpressing T cells showed CD62Lhi central memory-like (Tcm) phenotype with reduced glucose uptake (2-NBDGlo) and effector function (IFNγlo). Further, using tumor reactive T cells cultured in presence of recombinant Trx resulted in increased dependence of T cells on mitochondrial metabolism and led to improved tumor control. Thus, strategies to increase antioxidant capacity of anti-tumor T cells modulate its immune-metabolic phenotype leading to improved immunotherapeutic control of established tumors.

2021-12-20 | E-MTAB-7571 | biostudies-arrayexpress

Effects of redox modulation by inhibition of Thioredoxin reductase on radiosensitivity and gene expression

2010-12-03 | GSE25814 | GEO

Effects of redox modulation by inhibition of Thioredoxin reductase on radiosensitivity and gene expression

Project description:The involvement the thioredoxin system in radiation resistance was investigated in human lung cancer cells by a combination of ionizing radiation and specific thioredoxin reductase-inhibition by a phosphine gold compound. Gene expression profiles (Human Gene 1.0 ST) of lung cancer cells subjected to ionizing radiation and/or inhibition of thioredoxin reductase were studied. Data analyses were performed using the Affymetrix GeneChip Operating Software (GCOS) Version 1.4.

2010-12-03 | E-GEOD-25814 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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