Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease

ABSTRACT: SCD had hemolysis with elevated levels of heme and iron, which induced ferroptosis. Here, we found Nrf2 knockout in SCD mice accumulated the levels of the metabolite L-2-hydroxyglutarate (L2HG), which impaired ferroptosis stress response to exacerbate SCD symptom. Mechanistically, L2HG was found to regulate the expression of genes involved in the iron and heme metabolism via histone epigenetic hypermethylation. Our findings indicate an important role of Nrf2/L2HG in SCD for ferroptosis response.

ORGANISM(S): Mus musculus

PROVIDER: GSE188695 | GEO | 2021/11/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease [ChIP]

Project description:SCD had hemolysis with elevated levels of heme and iron, which induced ferroptosis. Here, we found Nrf2 knockout in SCD mice accumulated the levels of the metabolite L-2-hydroxyglutarate (L2HG), which impaired ferroptosis stress response to exacerbate SCD symptom. Mechanistically, L2HG was found to regulate the expression of genes involved in the iron and heme metabolism via histone epigenetic hypermethylation. Our findings indicate an important role of Nrf2/L2HG in SCD for ferroptosis response.

2023-03-02 | GSE225966 | GEO

Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease [ChIP-seq]

2023-03-02 | GSE223911 | GEO

Dimethyl fumarate increases fetal hemoglobin, provides heme detoxification, and corrects anemia in sickle cell disease

Project description:Sickle cell disease (SCD) results from a point mutation in the β-globin gene forming hemoglobin S (HbS), which polymerizes in deoxygenated erythrocytes, triggering recurrent painful vaso-occlusive crises and chronic hemolytic anemia. Reactivation of fetal Hb (HbF) expression ameliorates these symptoms of SCD. Nuclear factor (erythroid derived-2)–like 2 (Nrf2) is a transcription factor that triggers cytoprotective and antioxidant pathways to limit oxidative damage and inflammation and increases HbF synthesis in CD34+ stem cell–derived erythroid progenitors. We investigated the ability of dimethyl fumarate (DMF), a small-molecule Nrf2 agonist, to activate γ-globin transcription and enhance HbF in tissue culture, murine and primate models. DMF recruited Nrf2 to the γ-globin promoters and the locus control region of the β-globin locus in erythroleukemia cells, elevated HbF in SCD donor–derived erythroid progenitors, and reduced hypoxia-induced sickling. Chronic DMF administration in SCD mice induced HbF and increased Nrf2-dependent genes to detoxify heme and limit inflammation. This improved hematological parameters, reduced plasma-free Hb, and attenuated inflammatory markers. Chronic DMF administration to nonanemic primates increased γ-globin mRNA in BM and HbF protein in red cells. DMF represents a potential therapy for SCD to induce HbF and augment vasoprotection and heme detoxification

2017-11-01 | GSE105035 | GEO

Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease

Project description:Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease

| PRJNA779947 | ENA

The effect of the modulation of L2-hydroxyglutarate content in pachytene-diplotene cells of male mice

Project description:We found that testis of male mice contain high concentrations of L2-hydroxyglutarate (L2HG) specifically in germ cells at pachytene/ diplotene (PD) stage of spermatogenesis. In order to elucidate the function of 2HG we decreased its level by incubating PD cells with 24 mM oxamate and to rescue the putative phenotype by incubation with 24 mM oxamate together with 0.3 mM cell permeable L2HG.

2024-03-25 | GSE169015 | GEO

Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease [ChIP]

Project description:Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease [ChIP]

| PRJNA938119 | ENA

Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease [ChIP-seq]

Project description:Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease [ChIP-seq]

| PRJNA929025 | ENA

RNA-Seq analysis of classical monocyte in pateints with sickle cell disease [RNA-Seq]

Project description:Patients with sickle cell disease (SCD) suffer from intravascular hemolysis associated vascular injury and tissue damage. Classical monocytes (CMo), which comprise most blood circulating monocytes. are activated in SCD, but the cause and consequences of activation is less clear. Using transcriptome analysis, we found upregulation of the type I Interferon (IFN) pathway in sort-purified SCD CMo.

2021-11-10 | GSE168532 | GEO

Deviated myeloid differentiation in SCD mice under heme stress II.

Project description:Heme is an erythrocyte-derived toxin that drives disease progression in hemolytic anemias. During hemolysis, specialized bone marrow-derived macrophages with a high heme-metabolism capacity orchestrate disease adaptation by removing damaged erythrocytes and heme-protein complexes from the blood and supporting iron recycling for erythropoiesis. Here, we performed single-cell RNA sequencing with RNA velocity analysis of GM-CSF-supplemented mouse bone marrow cultures to assess myeloid differentiation under heme stress. We found that heme-activated NRF2 signaling shifted the differentiation trajectories of cells towards antioxidant, iron-recycling macrophages at the expense of dendritic cells, as these cells were selectively deficient in heme-exposed bone marrow cultures. Heme eliminated the capacity of GM-CSF-supplemented bone marrow cultures to activate antigen-specific T cells. The generation of functionally competent dendritic cells was restored by NRF2 loss. The heme-induced phenotype was reproduced in hemolytic mice with sickle cell disease and spherocytosis and associated with reduced dendritic cell functions in the spleen. Our data provide a novel mechanistic underpinning how hemolytic stress may provoke hyposplenism-related secondary immunodeficiency, which is a critical determinant of mortality in patients with genetic hemolytic anemias.

2022-01-25 | GSE179364 | GEO

Deviated myeloid differentiation in SCD mice under heme stress I.

2022-01-25 | GSE179363 | GEO