Hypoxia and ferroptosis

Cellular Signalling, Год журнала: 2024, Номер 122, С. 111328 - 111328

Опубликована: Авг. 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

Язык: Английский

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Iron chelators loaded on myocardiocyte mitochondria-targeted nanozyme system for treating myocardial ischemia-reperfusion injury in mouse models

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 15, 2025

Ferroptosis plays a critical role in myocardial ischemia-reperfusion injury (MIRI), posing significant clinical challenge. Nanoenzymes like cerium oxide (CeO2) hold promise for mitigating oxidative damage and inhibiting ferroptosis, but their delivery efficiency biological activity require optimization. This study aims to develop targeted nanozyme system MIRI treatment by integrating CeO2 with mesoporous polydopamine (mPDA) dexrazoxane (DXZ) achieve synergistic therapeutic effects. A biomineralization technique was used synthesize nanoparticles (2–3 nm) within mPDA, forming ~ 130 nm composite (Ce@mPDA). Surface modifications cardiac homing peptide (CHP) triphenylphosphine (TPP) enabled hierarchical targeting injured myocardium mitochondria. DXZ-loaded Ce@mPDA-C/P (D/Ce@mPDA-C/P) were evaluated vitro mouse model effects on stress, apoptosis, inflammation, function. D/Ce@mPDA-C/P exhibited robust ROS scavenging, sustained DXZ release, efficient mitochondrial targeting. The significantly reduced upregulated GPX4 expression, inhibited modulated the inflammatory microenvironment. Long-term studies demonstrated reductions fibrosis improvements function, including enhanced fractional shortening ejection fraction. effectively combines antioxidant properties of iron-chelating DXZ, providing promising strategy MIRI. approach may expand use advance nanomedicine-based interventions repair.

Язык: Английский

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Exosome‐Derived CDC42 From Hypoxia‐Pretreated Neural Stem Cells Inhibits ACSL4‐Related Ferroptosis to Alleviate Vascular Injury in Parkinson's Disease Mice Models

Journal of Neurochemistry, Год журнала: 2025, Номер 169(3)

Опубликована: Март 1, 2025

ABSTRACT Parkinson's disease (PD) is a neurodegenerative disorder that gets exacerbated by vascular injury. Neural stem cell‐derived exosomes (NSC‐Exos) display effective neuroprotective properties in PD models. Cell division control protein 42 (CDC42) connected to angiogenesis, but its effects remain undefined. This research aims reveal the role of CDC42 PD. First, we applied 1‐methyl‐4‐phenylpyridinium (MPP + ) induce human cerebral microvascular endothelial cells (HCMECs) model and evaluated cell viability ferroptosis. Then, characterized NSC‐Exos. Next, appraise effect hypoxia‐pretreated NSC‐Exos (H‐NSC‐Exos) on MPP ‐induced model, examined angiogenesis ferroptosis HCMECs. Moreover, constructed mice using 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) tested behavioral experiments injury mice. Furthermore, cellular after knockdown CDC42. Additionally, investigated interaction with Acyl‐CoA synthetase long‐chain family member 4 (ACSL4) detected overexpression ACSL4. We found H‐NSC‐Exos reversed decrease HCMECs migration, lowered lipid‐reactive oxygen species (lipid‐ROS) levels, suppressed ferroptosis, facilitated angiogenesis. attenuated MPTP‐induced development, injury, reduced raised lipid‐ROS which were ferrostatin‐1 liproxstatin‐1. interacted ACSL4 aggravated above was knocked down. Our study reveals H‐NSC‐Exos‐derived inhibited ACSL4‐related alleviate may serve as potent therapeutic target for treatment. image

Язык: Английский

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Upregulation of GPX4 drives ferroptosis resistance in scleroderma skin fibroblasts

Free Radical Biology and Medicine, Год журнала: 2024, Номер 221, С. 23 - 30

Опубликована: Май 11, 2024

Язык: Английский

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LASS2 suppresses metastasis in multiple cancers by regulating the ferroptosis signalling pathway through interaction with TFRC

Cancer Cell International, Год журнала: 2024, Номер 24(1)

Опубликована: Фев. 28, 2024

Abstract Background As a key enzyme in ceramide synthesis, longevity assurance homologue 2 (LASS2) has been indicated to act as tumour suppressor variety of cancers. Ferroptosis is involved processes; however, the role LASS2 regulating ferroptosis yet be explored. This article explores potential underlying mechanisms involved. Methods Bioinformatics tools and immunohistochemical staining were used evaluate expression, results analysed relation overall survival clinical association multiple Coimmunoprecipitation-coupled liquid chromatography-mass spectrometry (co-IP LC-MS) was performed identify LASS2-interacting proteins thyroid, breast, liver cancer cell lines. Transcriptomics, proteomics metabolomics analyses types using MS or LC–MS further explore Among these cells, common interaction partner transferrin receptor (TFRC) by protein–protein docking validated coimmunoprecipitation western blot, immunofluorescence, proximity ligation assays. Then, we experiments which cells treated with Fer-1 erastin left untreated, without inducing overexpression, assessed molecular biological cellular functions corresponding analyses. Results Low expression correlated adverse characteristic poor prognosis patients thyroid cancer, breast HCC. Multiomics revealed significant changes signalling pathway, iron ion transport homeostasis. Our vitro that overexpression regulated status affecting homeostasis, turn inhibited migration, invasion EMT. In addition, reversed metastasis induced either erastin. Mechanistically, interacts directly TFRC regulate homeostasis cells. Conclusions summary, our study reveals for first time can inhibit interacting metabolism influence suggest universal therapeutic targets treatment

Язык: Английский

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The Role of Nrf2 in the Regulation of Mitochondrial Function and Ferroptosis in Pancreatic Cancer

Antioxidants, Год журнала: 2024, Номер 13(6), С. 696 - 696

Опубликована: Июнь 6, 2024

The transcription factor nuclear erythroid 2-related 2 (Nrf2) represents the master regulator of cellular antioxidant response and plays a critical role in tumorigenesis. This includes preventive effect Nrf2 on cell death through ferroptosis, which an essential mechanism therapy resistance malignant tumors, such as pancreatic ductal adenocarcinoma (PDAC) one most aggressive still incurable tumors. Addressing this issue, we provide overview mediated with particular emphasis its mitochondria organelle responsible for execution ferroptosis. We further outline how deregulated adds to progression PDAC, especially respect ferroptosis anti-cancer drug killing is impaired by resistance. Our review discusses recent approaches inhibition natural synthetic compounds overcome based enhanced Finally, outlook therapeutic strategies combined inducing drugs.

Язык: Английский

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The potential roles of HIF-1α in epithelial-mesenchymal transition and ferroptosis in tumor cells

Cellular Signalling, Год журнала: 2024, Номер 122, С. 111345 - 111345

Опубликована: Авг. 10, 2024

In tumors, the rapid proliferation of cells and imperfect blood supply system lead to hypoxia, which can regulate adaptation tumor hypoxic environment through hypoxia-inducible factor-1α (HIF-1α) promote development in multiple ways. Recent studies have found that epithelial-mesenchymal transition (EMT) ferroptosis play important roles progression cells. The activation HIF-1α is considered a key factor inducing EMT When activated, it EMT-related genes, causing gradually lose their epithelial characteristics acquire more invasive mesenchymal traits. occurrence allows better adapt changes surrounding tissue, enhancing migratory capabilities, thus promoting progression. At same time, also plays crucial regulatory role environment, may affect processes such as iron metabolism oxidative stress responses, This article briefly reviews dual cells, helping gain deeper understanding pathways providing new perspective for pathogenesis tumors. regulation become an strategy future therapy.

Язык: Английский

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Ferroptosis and myocardial ischemia-reperfusion: mechanistic insights and new therapeutic perspectives

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Окт. 1, 2024

Myocardial ischemia-reperfusion injury (MIRI) is a significant factor in the development of cardiac dysfunction following myocardial infarction. Ferroptosis, type regulated cell death driven by iron and marked lipid peroxidation, has garnered growing interest for its crucial involvement pathogenesis MIRI.This review comprehensively examines mechanisms ferroptosis, focusing on regulation through metabolism, VDAC signaling, antioxidant system dysregulation. We also compare ferroptosis with other forms to highlight distinct characteristics. Furthermore, MIRI examined focus recent discoveries concerning ROS generation, mitochondrial impairment, autophagic processes, ER stress, non-coding RNA regulation. Lastly, emerging therapeutic strategies that inhibit mitigate are reviewed, providing new insights into potential clinical applications.

Язык: Английский

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Targeting ferroptosis: a promising approach for treating lung carcinoma

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Янв. 29, 2025

Abstract Lung carcinoma incidence and fatality rates remain among the highest on a global scale. The efficacy of targeted therapies immunotherapies is commonly compromised by emergence drug resistance other factors, resulting in lack durable therapeutic benefits. Ferroptosis, distinct pattern cell death marked buildup iron-dependent lipid peroxides, has been shown to be novel potentially more effective treatment for lung carcinoma. However, mechanism regulatory network ferroptosis are exceptionally complex, many unanswered questions remain. In addition, research diagnosis cancer growing exponentially. Therefore, it necessary provide thorough summary latest advancements field ferroptosis. Here, we comprehensively analyze mechanisms underlying preconditions ferroptosis, defense system, associated molecular networks. potential strategies also highlighted. Targeting improves tumor enhances effectiveness drugs immunotherapies. These findings may shed fresh light management carcinoma, as well development related

Язык: Английский

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Crosstalk Between Autophagy and Other Forms of Programmed Cell Death

European Journal of Pharmacology, Год журнала: 2025, Номер 995, С. 177414 - 177414

Опубликована: Фев. 20, 2025

Cell death occurs continuously throughout individual development. By removing damaged or senescent cells, cell not only facilitates morphogenesis during the developmental process, but also contributes to maintaining homeostasis after birth. In addition, reduces spread of pathogens by eliminating infected cells. is categorized into two main forms: necrosis and programmed death. Programmed encompasses several types, including autophagy, pyroptosis, apoptosis, necroptosis, ferroptosis, PANoptosis. Autophagy, a mechanism that maintains cellular equilibrium via breakdown reutilization proteins organelles, implicated in regulating almost all forms pathological contexts. Notably, PANoptosis are directly classified as autophagy-mediated Therefore, autophagy presents therapeutic approach for treating diseases such inflammation tumors arise from abnormalities other This review focuses on crosstalk between modalities, providing new perspectives clinical interventions inflammatory neoplastic diseases.

Язык: Английский

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