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Glutaminolysis fuels de novo glutathione synthesis, regulates redox homeostasis and directs T cell differentiation

ABSTRACT: We reveal that dimethyl fumarate, a FDA approved drug (BG-12/Tecfidera) for multiple sclerosis, suppresses TH17 differentiation by augmenting intracellular ROS

ORGANISM(S): Mus musculus

PROVIDER: GSE98733 | GEO | 2018/05/01

REPOSITORIES: GEO

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MYCN drives glutaminolysis in neuroblastoma and confers sensitivity to ROS augmenting agents

Project description:Through a small scale metabolic-modulator screening, we have identified dimethyl fumarate (DMF), a FDA approved drug for multiple sclerosis, which suppresses neuroblastoma cell growth in vitro and in vivo. Mechanistically, DMF suppresses neuroblastoma cell growth through inducing ROS and subsequently suppressing MYCN expression.

2018-04-18 | GSE98241 | GEO

Histone modification and RNA changes in macrophages exposed to Beta-glucan and Fumarate

Project description:Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as Beta glucan. We apply an epigenomic approach to characterize the molecular events involved in fumarate or BG induced trained innate immunity. ChIP-seq and RNA-seq data were generated. This analysis identified epigenetic programs in trained macrophages, with fumarate exposure inducing a small subset of BG-induced histone acetylation and methylation changes.

2016-11-01 | GSE86940 | GEO

Expression data of renal cancer cell treated with Oncolytic virus VSVd51 and Fumaric acid esters such as Dimethyl fumarate

Project description:We propose a strategy to boost the therapeutic efficacy of Oncolytic therapy by combining it with fumaric acid ester such as Dimethyl fumarate (DMF) The mechanism of action was examined by microarray analysis using the Affymetrix Human PrimeView Array.

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Chemical proteomic map of dimethyl fumarate-sensitive cysteines in primary human T cells

Project description:Primary human and mouse T cells were treated with the multiple sclerosis drug dimethyl fumarate (DMF) or its in vivo metabolite monomethyl fumarate (MMF). Cysteines sensitive to DMF or MMF were identified using iodoacetamide alkyne enrichment.

2016-08-31 | MSV000080111 | MassIVE

Treatment of chronic lymphocytic leukemia cells with signaling inhibitors

Project description:To identify the molecular targets of treatment, we studied gene expression profile of primary chronic lymphocytic leukemia (CLL) cells isolated from the peripheral blood of CLL patients and treated in vitro with two distinct signaling inhibitors: 1) Dimethyl fumarate targeting inflammatory pathways 2) VIVIT peptide targeting NFAT transcription factor activation.

2024-03-14 | GSE245432 | GEO

Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats

Project description:Inflammation and oxidative stress have been implicated in the pathogenesis of metabolic disturbances. Esters of fumaric acid, mainly dimethyl fumarate (DMF), exhibit immunomodulatory, anti-inflammatory, and anti-oxidative effects. In the current study, we tested the hypothesis that fumaric acid ester treatment of an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP), will ameliorate inflammation, oxidative stress, and metabolic disturbances.

2015-12-31 | E-MTAB-2406 | biostudies-arrayexpress

Project description:Global studies of A375 cells treated with dimethyl fumarate and vemurafenib

| PRJNA769791 | ENA

Glutathione de novo synthesis but not recycling process coordinates with glutamine catabolism to control redox homeostasis and directs murine T cell differentiation.

Project description: Not available

| S-EPMC6152796 | biostudies-literature

Dimethyl fumarate induces ferroptosis and impairs NF-κB/STAT3 signaling in DLBCL

Project description:Dimethyl fumarate induces ferroptosis and impairs NF-κB/STAT3 signaling in DLBCL

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Transcriptomic analysis of fumarate compounds identifies unique effects of isosorbide di-(methyl fumarate) on NRF2, NF-kappaB and IRF1 pathway genes

Project description:Dimethyl fumarate (DMF) has emerged as first-line therapy for relapsing-remitting multiple scle-rosis (RRMS). This treatment, however, has been limited by adverse effects, which has prompted development of novel derivatives with improved tolerability. We compared effects of fumarates on gene expression in astrocytes. Our analysis included diroximel fumarate (DRF) and its metabolite monomethyl fumarate (MMF), along with a novel compound isosorbide di-(methyl fumarate) (IDMF). Treatment with IDMF resulted in the largest number of differentially expressed genes. The effects of DRF and MMF were consistent with NRF2 activation and NF-kappaB inhibition, respectively. IDMF responses, however, were concordant with both NRF2 activation and NF-kappaB inhibition, and we confirmed IDMF-mediated NF-kappaB inhibition using a reporter assay. IDMF also down-regulated IRF1 expression and IDMF-decreased gene promoters were enriched with IRF1 recognition se-quences. Genes altered by each fumarate overlapped significantly with those near loci from MS genetic association studies, but IDMF had the strongest overall effect on MS-associated genes. These results show that next-generation fumarates such as DRF and IDMF have effects differing from those of the MMF metabolite. Our findings support a model in which IDMF attenuates oxidative stress via NRF2 activation, with suppression of NF-kappaB and IRF1 contributing to mitigation of in-flammation and pyroptosis.

2022-04-27 | GSE200539 | GEO

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