Ferroptosis inhibition by oleic acid mitigates iron-overload-induced injury
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ABSTRACT:
PROVIDER: PRJNA1020416 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26156477_1.fastq.gz | Fastqsanger.gz | |||
| SRR26156477_2.fastq.gz | Fastqsanger.gz | |||
| SRR26156478_1.fastq.gz | Fastqsanger.gz | |||
| SRR26156478_2.fastq.gz | Fastqsanger.gz | |||
| SRR26156479_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Iron overload, characterized by accumulation of iron in tissues, induces a multiorgan toxicity whose mechanisms are not fully understood. Using cultured cell lines, Caenorhabditis elegans, and mice, we found that ferroptosis occurs in the context of iron-overload-mediated damage. Exogenous oleic acid protected against iron-overload-toxicity in cell culture and Caenorhabditis elegans by suppressing ferroptosis. In mice, oleic acid protected against FAC-induced liver lipid peroxidation and damage. Oleic acid changed the cellular lipid composition, characterized by decreased levels of polyunsaturated fatty acyl phospholipids and decreased levels of ether-linked phospholipids. The protective effect of oleic acid in cells was attenuated by GW6471 (a PPAR- antagonist), as well as in Caenorhabditis elegans lacking the nuclear hormone receptor NHR-49 (a PPAR- functional homologue). These results highlight ferroptosis as a driver of iron-overload-mediated damage, which is inhibited by oleic acid. This monounsaturated fatty acid represents a potential therapeutic approach to mitigating organ damage in iron overload individuals.
2023-10-02 | GSE243891 | GEO
Project description:Iron overload, characterized by accumulation of iron in tissues, induces a multiorgan toxicity whose mechanisms are not fully understood. Using cultured cell lines, Caenorhabditis elegans, and mice, we found that ferroptosis occurs in the context of iron-overload-mediated damage. Exogenous oleic acid protected against iron-overload-toxicity in cell culture and Caenorhabditis elegans by suppressing ferroptosis. In mice, oleic acid protected against FAC-induced liver lipid peroxidation and damage. Oleic acid changed the cellular lipid composition, characterized by decreased levels of polyunsaturated fatty acyl phospholipids and decreased levels of ether-linked phospholipids. The protective effect of oleic acid in cells was attenuated by GW6471 (a PPAR-? antagonist), as well as in Caenorhabditis elegans lacking the nuclear hormone receptor NHR-49 (a PPAR-? functional homologue). These results highlight ferroptosis as a driver of iron-overload-mediated damage, which is inhibited by oleic acid. This monounsaturated fatty acid represents a potential therapeutic approach to mitigating organ damage in iron overload individuals.
2025-05-06 | PXD045642 | Pride
Project description:Iron overload, characterized by accumulation of iron in tissues, induces a multiorgan toxicity whose mechanisms are not fully understood. Using cultured cell lines, Caenorhabditis elegans, and mice, we found that ferroptosis occurs in the context of iron-overload-mediated damage. Exogenous oleic acid protected against iron-overload-toxicity in cell culture and Caenorhabditis elegans by suppressing ferroptosis. In mice, oleic acid protected against FAC-induced liver lipid peroxidation and damage. Oleic acid changed the cellular lipid composition, characterized by decreased levels of polyunsaturated fatty acyl phospholipids and decreased levels of ether-linked phospholipids. The protective effect of oleic acid in cells was attenuated by GW6471 (PPAR-α antagonist), as well as in Caenorhabditis elegans lacking the nuclear hormone receptor NHR-49 (a PPAR-α functional homologue). These results highlight ferroptosis as a driver of iron-overload-mediated damage, which is inhibited by oleic acid. This monounsaturated fatty acid represents a potential therapeutic approach to mitigating organ damage in iron overload individuals.
| S-EPMC10922137 | biostudies-literature
Project description:Acute iron overload leads to ferroptosis, in a mouse model of FeSO4 challenge causing lethal shock, associated with inflammation and multiple organ failure (MOF). We investigated molecular aspects causing this phenomenon upon FeSO4 overload, with a focus on the glucocorticoid receptor (GR), an important anti-inflammatory transcription factor. We report that Fe overload activates the HPA axis, leading to corticosterone increases in the blood, acutely causing upregulation of GR-dependent genes in liver. Since a GR blocker, mutant GR mice and removal of adrenals sensitize mice for Fe-induced toxicity, GR appears essential to resist ferroptosis, and stimulation appears an interesting option to deal with ferroptosis. However, DEX treatment is unable to protect mice against FeSO4- induced death and MOF. This dilemma is shown, by RNA-seq, to be the result of a quick and complete inactivation of GR biological function by Fe2+, shortly after the initial activation. This inactivity of GR seems to be the result of a complete lack of GR to bind ligand. We discuss the possible mechanism and complications for ferroptosis progression during diseases
2025-04-30 | GSE290955 | GEO
Project description:Hereditary hemochromatosis and transfusional iron overload are frequent clinical conditions associated with progressive iron accumulation in parenchymal tissues leading to eventual organ failure. We have discovered a novel mechanism to reverse iron overload by pharmacological modulation of the divalent metal transporter-1 (DMT-1). DMT-1 mediates intracellular iron transport during the transferrin cycle and apical iron absorption in the duodenum. Additional functions in iron handling in the kidney and liver are less well understood. We show that the L- type calcium-channel blocker nifedipine increases DMT-1 mediated cellular iron transport 10-to 100-fold at concentrations between 1-100 uM. Mechanistically, nifedipine causes this effect by prolongation of the activity of DMT-1 to transport iron. We show that nifedipine mobilizes iron from the liver of mice with primary and secondary iron overload, and enhances urinary iron excretion. Modulation of DMT-1 function by L-type calcium-channel blockers emerges a novel pharmacological concept to treat iron overload disorders.<br> <br> In this experiment mice were subjected to dietary iron overload before being treated with nifedipine at 5 ug/g bodyweight, or mock treated with the same volume of solvent.
2007-03-01 | E-MEXP-982 | biostudies-arrayexpress
Project description:Iron overload disorders are an important factor contributing to various pathologies. However, the effects of iron overload on liver transcriptional regulation are largely unknown. To examine the effects of iron overload on liver transcriptome and chromatin accessibility, we fed mice a high-iron diet (HID) for 2 weeks. Then, livers were collected and profiled by RNA-seq and ATAC-seq.
2023-06-24 | GSE224000 | GEO
Project description:RATIONALE: Deferasirox may remove excess iron from the body caused by blood transfusions.
PURPOSE: This clinical trial studies deferasirox in treating iron overload caused by blood transfusions in patients with hematologic malignancies.
| 2100588 | ecrin-mdr-crc
Project description:Iron overload causes the generation of reactive oxygen species, which can lead to lasting damage to the liver and other organs. We studied the effects of iron deficiency and iron overload on the hepatic transcriptional and metabolomic profile in mouse models.
2018-02-13 | GSE86236 | GEO
Project description:Liver immune homeostasis relies on the coordinated actions of various immune cells including dendritic cells (DCs), which exert regulatory roles in both innate and adaptive immunity. Various pieces of evidence demonstrate that the properties of immune cells are highly influenced by iron metabolism. However, the roles of iron metabolism on DC function remain poorly understood. Here, we show that mice with iron overload in DCs displayed worsening of liver injury and mortality in acetaminophen (APAP) -induced acute hepatitis. Enhanced neutrophil infiltration was observed in these mice during the progression of liver injury. DCs with iron overload showed increased expression of the neutrophil-attracting cytokine IL-6, thereby accelerating liver injury. Mechanistic studies revealed that iron enhanced the recruitment of NF-κB to the IL-6 promoter upon TLR4 activation. Our findings provide an insight into the regulatory mechanisms by which iron metabolism influences DC function. This study also highlights the critical role of the DC-IL-6-neutrophil axis in acute liver injury.
2025-05-22 | GSE284273 | GEO
Project description:Acute liver failure is a critical clinical issue in liver diseases, characterized by extensive hepatocyte death involving various mechanisms, including apoptosis, necroptosis, and ferroptosis. Ferroptosis, an iron-dependent form of non-apoptotic cell death marked by significant lipid peroxidation, plays a crucial role in the pathogenesis of multiple liver disorders.This cell death results in elevated levels of acute phase proteins synthesized and secreted by the liver. While previous studies indicated that the ORM2 protein does not directly influence apoptotic signaling pathways, our findings reveal that its knockout in acute liver injury models significantly worsens damage and reduces the median survival time of mice. In contrast, liver-specific overexpression of Orm2 markedly mitigates acute liver injury.We found that Orm2 exerts its protective effects by non-competitively binding to NCOA4, inhibiting ferroautophagy, and reducing iron ion accumulation, thereby decreasing ferroptosis during acute liver injury. Additionally, interference with TAX1BP1 gene expression compensates for the increased sensitivity to ferroptosis resulting from Orm2 knockdown. Importantly, ORM2 infusion therapy protects against acute damage in various organs, including the liver. Mechanistically, ORM2 in plasma enters damaged cells via endocytosis, regulating iron homeostasis and alleviating acute injury caused by ferroptosis.In summary, Orm2 is a potential protective factor against abnormal iron accumulation and ferroptosis, reducing acute organ damage. These findings suggest that acute phase proteins may play a role in cellular resistance to death during organ injury and offer a potential adjunctive therapeutic strategy for acute organ damage caused by ferroptosis.
2024-09-22 | GSE277619 | GEO