Tumor associated macrophages transfer ceruloplasmin mRNA to fibrosarcoma cells and protect them from ferroptosis

Redox Biology, Journal Year: 2024, Volume and Issue: 71, P. 103093 - 103093

Published: Feb. 17, 2024

Solid tumors are characterized by hypoxic areas, which prone for macrophage infiltration. Once infiltrated, macrophages polarize to tumor associated (TAM) support progression. Therefore, the crosstalk between TAMs and cells is of current interest development novel therapeutic strategies. These may comprise induction an iron- lipid peroxidation-dependent form cell death, known as ferroptosis. To study - we polarized primary human towards a TAM-like phenotype, co-cultured them with HT1080 fibrosarcoma cells, analyzed response ferroptosis induction. In expression ceruloplasmin mRNA increased, was driven hypoxia inducible factor 2 signal transducer activator transcription 1. Subsequently, transferred from via extracellular vesicles. translated into protein protect RSL3-induced Mechanistically this based on reduced iron abundance peroxidation. Interestingly, in naïve also induced under co-culture recapitulated protective effect observed TAM co-cultures. conclusion, provoke release thereby peroxidation/ferroptosis.

Language: Английский

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Hypoxia and ferroptosis

Cellular Signalling, Journal Year: 2024, Volume and Issue: 122, P. 111328 - 111328

Published: Aug. 1, 2024

Ferroptosis is a novel, iron-dependent cell death characterized by the excessive accumulation of ferroptosis lipid peroxides ultimately leading to oxidative damage membrane. Iron, lipid, amino acid metabolism, and other signaling pathways all control ferroptosis. Numerous bodily tissues experience hypoxia under normal pathological circumstances. Tissue cells can adjust these changes activating hypoxia-inducible factor (HIF) pathway mechanisms in response hypoxic environment. In recent years, there has been increasing evidence that are closely linked, regulate specific conditions through different pathways. this paper, we review possible positive negative regulatory factors, as well ferroptosis-associated ischemic diseases, with intention delivering novel therapeutic avenues for defense management illnesses linked

Language: Английский

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Hypoxia induces ferroptotic cell death mediated by activation of the inner mitochondrial membrane fission protein MTP18/Drp1 in invertebrates

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108326 - 108326

Published: Feb. 1, 2025

Hypoxia and ischemia damage sensitive organelles such as mitochondria, thus mitochondrial dysfunction contributes to metabolic disorders in crustaceans under hypoxia. The mechanisms associated with ferroptosis hypoxic have not been determined crustaceans. In particular, the early molecular events of dynamics require clarification. this study, two evolutionarily conserved fission proteins, Drp1 MTP18, were identified oriental river prawn (Macrobrachium nipponense). vitro, ferroptosis-mediated impairment membrane potential was induced by hypoxia hemocytes. hypoxia-induced hemocytes, activation increased phosphorylation at S616 identified. translocation also increased, fusion-related protein expression decreased vivo. Altered fission-fusion linked dysfunction, inducing a classic mechanism. Marf overexpression or knockdown protected against ferroptotic cell death vitro. Furthermore, verified be driven Drp1/MTP18 interaction. Under hypoxia, MTP18 transcription binding activated HIF-1α response elements (HREs) its promoter. Conjointly, resulted less apoptosis mortality gill tissue vitro; suggesting that adaptation involves vital function MTP18. conclusion, we uncovered role death. Therefore, suggest specific modulation MTP18/DRP1-mediated might therapeutic strategy stress-induced injury invertebrates.

Language: Английский

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Molecular regulation and therapeutic implications of cell death in pulmonary hypertension

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: July 12, 2023

Abstract Pulmonary hypertension (PH) is a clinical and pathophysiological syndrome caused by changes in pulmonary vascular structure or function that results increased resistance arterial pressure, it characterized endothelial dysfunction, artery media thickening, remodeling, right ventricular hypertrophy, all of which are driven an imbalance between the growth death cells. Programmed cell (PCD), different from necrosis, active cellular mechanism activated response to both internal external factors precisely regulated More than dozen PCD modes have been identified, among apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis, cuproptosis proven be involved pathophysiology PH varying degrees. This article provides summary regulatory patterns their potential effects on PH. Additionally, describes current understanding this complex interconnected process analyzes therapeutic targeting specific as molecular targets.

Language: Английский

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A critical appraisal of ferroptosis in Alzheimer’s and Parkinson’s disease: new insights into emerging mechanisms and therapeutic targets

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 8, 2024

Neurodegenerative diseases represent a pressing global health challenge, and the identification of novel mechanisms underlying their pathogenesis is utmost importance. Ferroptosis, non-apoptotic form regulated cell death characterized by iron-dependent lipid peroxidation, has emerged as pivotal player in neurodegenerative diseases. This review delves into discovery ferroptosis, critical players involved, intricate role neurodegeneration, with an emphasis on Alzheimer’s Parkinson’s We critically appraise unsolved mechanistic links involved initiation propagation such signaling cascade resulting de-repression lipoxygenase translation played mitochondrial voltage-dependent anionic channels iron homeostasis. Particular attention given to dual heme oxygenase which may be linked non-specific activity P450 reductase endoplasmic reticulum. Despite limited knowledge ferroptosis progression Nrf2/Bach1 target genes have crucial defenders anti-ferroptotic pathways. The activation Nrf2 inhibition Bach1 can counteract present promising avenue for future therapeutic interventions targeting

Language: Английский

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Oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles attenuates gastric and small intestinal mucosal ferroptosis caused by hypoxia through inhibiting HIF-1α- and HIF-2α-mediated lipid peroxidation

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 12, 2024

Abstract The prevention and treatment of gastrointestinal mucosal injury caused by a plateau hypoxic environment is clinical conundrum due to the unclear mechanism this syndrome; however, oxidative stress microbiota dysbiosis may be involved. Robinia pseudoacacia L. flower, homologous functional food, exhibits various pharmacological effects, such as antioxidant, antibacterial, hemostatic activities. An increasing number studies have revealed that plant exosome-like nanoparticles (PELNs) can improve intestinal exert antioxidant effects. In study, oral administration flower (RFELNs) significantly ameliorated hypoxia-induced gastric small in mice downregulating hypoxia-inducible factor-1α (HIF-1α) HIF-2α expression inhibiting hypoxia-mediated ferroptosis. addition, RFELNs partially improved microbial metabolic disorders stomach intestine. Notably, displayed specific targeting tract. vitro experiments using epithelial cell lines showed death elevated HIF-1α under 1% O 2 mainly occurred via obviously inhibited downregulated NOX4 ALOX5, which drive reactive oxygen species production lipid peroxidation, respectively, suppressing ferroptosis hypoxia. conclusion, our findings underscore potential novel, naturally derived agents tract, providing promising therapeutic approach for Graphical

Language: Английский

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The Regulation of Ferroptosis by Noncoding RNAs

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13336 - 13336

Published: Aug. 28, 2023

As a novel form of regulated cell death, ferroptosis is characterized by intracellular iron and lipid peroxide accumulation, which different from other death forms morphologically, biochemically, immunologically. Ferroptosis metabolism, antioxidant defense systems as well various transcription factors related signal pathways. Emerging evidence has highlighted that associated with many physiological pathological processes, including cancer, neurodegeneration diseases, cardiovascular ischemia/reperfusion injury. Noncoding RNAs are group functional RNA molecules not translated into proteins, can regulate gene expression in manners. An increasing number studies have shown noncoding RNAs, especially miRNAs, lncRNAs, circRNAs, interfere the progression modulating ferroptosis-related genes or proteins directly indirectly. In this review, we summarize basic mechanisms regulations focus on recent mechanism for types ncRNAs to conditions, will deepen our understanding regulation provide new insights employing ferroptosis-associated therapeutic strategies.

Language: Английский

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Sodium Butyrate Alleviates Free Fatty Acid-Induced Steatosis in Primary Chicken Hepatocytes via Regulating the ROS/GPX4/Ferroptosis Pathway

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 140 - 140

Published: Jan. 23, 2024

Fatty liver hemorrhagic syndrome (FLHS) in laying hens is a nutritional metabolic disease commonly observed high-yielding hens. Sodium butyrate (NaB) and ferroptosis were reported to contribute the pathogenesis of fatty liver-related diseases. However, underlying mechanism NaB FLHS whether it mediates remains unclear. A chicken primary hepatocyte induced by free acids (FFAs, keeping ratio sodium oleate palmitate concentrations at 2:1) was established, which received treatments with NaB, inducer RAS-selective lethal 3 (RSL3), inhibitor ferrostatin-1 (Fer-1). As result, increased biochemical lipid metabolism indices, antioxidant level, while inhibiting intracellular ROS accumulation activation signaling pathway, as evidenced reduction iron concentration, upregulated GPX4 xCT expression, inhibited NCOA4 ACSL4 expression. Furthermore, treatment Fer-1 reinforced protective effects RSL3 reversed blocking ROS/GPX4/ferroptosis leading droplets oxidative stress. Collectively, our findings demonstrated that protects hepatocytes regulating ROS/GPX4-mediated providing new strategy target for FLHS.

Language: Английский

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Spotlight on iron overload and ferroptosis: Research progress in female infertility

Life Sciences, Journal Year: 2023, Volume and Issue: 340, P. 122370 - 122370

Published: Dec. 22, 2023

Language: Английский

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Ferroptosis pathways: Unveiling the neuroprotective power of cistache deserticola phenylethanoid glycosides

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 333, P. 118465 - 118465

Published: June 27, 2024

Cistanche deserticola is a kind of parasitic plant living in the roots desert trees. It rare Chinese medicine, which has effect tonifying kidney Yang, benefiting essence and blood moistening intestinal tract. Cistache phenylethanoid glycoside (PGS), an active component found Ma, have potential tonifying, intellectual enhancing, neuroprotective effects. total capsule been marketed to treat vascular dementia disease. To identify renal, enhancing effects PGS explore exact targets mechanisms PGS. This study systematically investigated four types pathways leading ferroptosis through transcriptome, metabolome, ultrastructure molecular biology techniques explored mechanism by multiple synergistically exert on hypoxia. alleviated learning memory dysfunction pathological injury mice exposed hypobaric hypoxia attenuating hypoxia-induced hippocampal histopathological damage, impairing blood‒brain barrier integrity, increasing oxidative stress levels, expression cognitive proteins. reduced formation lipid peroxides improved upregulating GPX-4/SCL7A311 axis downregulating ACSL4/LPCAT3/LOX axis. also facilitating cellular Fe2+ efflux regulating mitochondrial transport effectively antagonized cell induced erastin (a inducer). demonstrated prevents hypoxic nerve pathways, achieved mice. provides theoretical basis for development application

Language: Английский

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