FOXO1‐NCOA4 Axis Contributes to Cisplatin‐Induced Cochlea Spiral Ganglion Neuron Ferroptosis via Ferritinophagy

Advanced Science, Год журнала: 2024, Номер 11(40)

Опубликована: Авг. 29, 2024

Abstract Mammalian cochlea spiral ganglion neurons (SGNs) are crucial for sound transmission, they can be damaged by chemotherapy drug cisplatin and lead to irreversible sensorineural hearing loss (SNHL), while such damage also render cochlear implants ineffective. However, the mechanisms underlying cisplatin‐induced SGNs subsequent SNHL still under debate there is no currently effective clinical treatment. Here, this study demonstrates that ferroptosis triggered in following exposure cisplatin. Inhibiting protects against loss, inducing intensifies these effects. Furthermore, prompts nuclear receptor coactivator 4 (NCOA4)‐mediated ferritinophagy SGNs, knocking down NCOA4 mitigates loss. Notably, upstream regulator of identified transcription factor forkhead box O1 (FOXO1) shown directly suppress expression SGNs. The FOXO1 amplifies NCOA4‐mediated ferritinophagy, increases lipid peroxidation, disrupting interaction between knock out mice prevents SGN Collectively, highlights critical role FOXO1‐NCOA4 axis regulating damage, offering promising therapeutic targets mitigation.

Язык: Английский

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Ferroptosis: iron release mechanisms in the bioenergetic process

Cancer and Metastasis Reviews, Год журнала: 2025, Номер 44(1)

Опубликована: Фев. 25, 2025

Язык: Английский

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Ferrostatin-1 improves acute sepsis-induced cardiomyopathy via inhibiting neutrophil infiltration through impaired chemokine axis

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Дек. 12, 2024

Introduction Sepsis-induced cardiomyopathy is a common complication of sepsis and associated with higher mortality. To date, effective diagnostic management strategies are still lacking. Recent studies suggest that ferroptosis plays critical role in sepsis-induced inhibitor Ferrostatin-1 (Fer-1) improved cardiac dysfunction survival lipopolysaccharide (LPS) induced endotoxemia. However, the effects Fer-1 early stages cecal ligation puncture (CLP) remains unclear. Our study aims to elucidate acute phase peritonitis injury. Methods Results CLP was used induce mice. Pretreatment ferrostatin-1 vivo models. Survival monitored for 48h. Cardiac function histology were analyzed 6h after surgery. We found ejection fraction (EF) remained normal at CLP, but contractility detected by muscle strain analysis significantly reduced, along increased immune cell infiltration. Pretreating mice 5 mg/kg reduced At key regulator Gpx4, iron malonaldehyde (MDA) did not change, marker gene expression increased. treatment showed beneficial function, less myocardial inflammatory cytokine inhibited cells, especially neutrophil infiltration heart. Consistently, chemokines (Ccrl2, Cxcl2, Cxcl3 Cxcl5) as well extracellular matrix (ECM) degradation enzymes (Adamts1, Adamts4, Adamts9 Mmp8) decreased pre-treated Conclusion Discussion findings inhibits disrupting chemokine axis, highlighting its potential therapeutic option manage overactivation cardiomyopathy.

Язык: Английский

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SIRT3 regulates PFKFB3-mediated glycolysis to attenuate cisplatin-induced ototoxicity both in vivo and in vitro

Archives of Toxicology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

Язык: Английский

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Transforming Growth Factor‐β‐Activated Protein 1 (TAK1) Regulates Necroptosis in Age‐Related Hearing Loss

Aging Cell, Год журнала: 2025, Номер unknown

Опубликована: Фев. 28, 2025

ABSTRACT Inflammation plays an important role in age‐related hearing loss (ARHL). Transforming growth factor‐β‐activated protein 1 (TAK1), a key factor upstream of inflammatory pathways, mediates various cell death potentially influencing the survival and cochlear hair cells. The DBA/2 J mouse model HEI‐OC1 line were used to investigate mechanism TAK1‐mediated inflammation ARHL. Hematoxylin eosin staining revealed significant histological damage cochlea 16‐week‐old mice, along with increase auditory‐evoked brainstem response thresholds. Concurrently, TAK1 mRNA levels decreased sharply, necroptosis significantly increased indicating correlation between expression, necroptosis, loss. We subsequently constructed knockdown overexpression cells for further investigation. activated necroptotic pathway, characterized by up‐regulation RIPK3 MLKL , down‐regulation NF‐κB Caspase 8 . However, successfully prevented cells, leading decreases treated inhibitors found that they could reverse caused This preliminary study shows pathways play pathogenesis

Язык: Английский

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Pinoresinol Diglucoside Attenuates Nuclear Receptor Coactivator 4‐Mediated Ferritinophagy Associated with Cisplatin‐Induced Hearing Loss

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

Cisplatin can cause irreversible hearing loss. However, effective approaches to its prevention are not established. In this study, the effect of traditional Chinese medicine monomer pinoresinol diglucoside (PDG) is evaluated on cisplatin-induced ototoxicity and underlying mechanism action. PDG significantly increases cell viability inhibits reactive oxygen species production ferroptosis in cisplatin-treated House Ear Institute-Organ Corti 1 cells basilar membranes. partially restores loss caused by cisplatin. Transcriptome sequencing identifies Suppressor Cytokine Signaling (SOCS1), which elevated cisplatin-only group but reduced after application. SOCS1 a ferroptosis-promoting factor, knocking it down nuclear receptor coactivator 4 (NCOA4) ferritinophagy. Transmission electron microscopy reveals that reduces number autophagic lysosomes induced Co-immunoprecipitation performed confirm interaction between NCOA4. Taken together, these results indicate NCOA4-mediated ferritinophagy downregulating SOCS1, ototoxicity. This study provides new clinical option for

Язык: Английский

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Ferroptosis regulation by traditional chinese medicine for ischemic stroke intervention based on network pharmacology and data mining

PLoS ONE, Год журнала: 2025, Номер 20(4), С. e0321751 - e0321751

Опубликована: Апрель 16, 2025

Objective The aim of this study is to use network pharmacology and data mining explore the role traditional Chinese medicine (TCM) in ischemic stroke (IS) intervention by ferroptosis regulation. results will provide reference for related research on IS. Methods ferroptosis-related targets were obtained from GeneCards, GeneCLiP3, FerrDdb databases, while IS sourced GeneCards DisGeNET databases. Venny was used identify associated with ferroptosis. A protein-protein interaction (PPI) analysis then conducted, machine learning screening validate these potential targets. that met specific criteria their compounds allowed us select TCMs. mechanistic conducted using DAVID database. PPI diagrams, target-compound target-compound-TCM diagrams constructed. Finally, molecular docking technology verify binding activities TCM core components identified In addition, properties, flavors, meridian tropism, therapeutic effects candidate TCMs analyzed statistically evaluated. Results total 706 obtained, 14 learning. Furthermore, 413 301 screened, prescriptions stable. primarily exhibited cold, warm, bitter taste, pungent liver meridian, heat-cleaning medicinal, tonify deficiency properties. Conclusions This investigated regulation TCM. We began investigating ferroptosis, we also relevant mechanism

Язык: Английский

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Targeting Programmed Cell Death in Acquired Sensorineural Hearing Loss: Ferroptosis, Necroptosis, and Pyroptosis

Neuroscience Bulletin, Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

Язык: Английский

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VDAC1 Inhibition Protects Against Noise‐Induced Hearing Loss via the PINK1/Parkin Pathway

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(4)

Опубликована: Апрель 1, 2025

ABSTRACT Aims This study examined the effect of 4,4′‐diisothiocyanostilbene‐2,2′‐disulfonic acid (DIDS), an anion channel blocker voltage‐dependent 1 (VDAC1), on noise‐induced hearing loss (NIHL) and its underlying mechanisms. Methods Cochlear explants House Ear Institute‐Organ Corti (HEI‐OC1) cells were used to assess DIDS in vitro. Auditory brainstem responses auditory functions mice. Immunofluorescence staining myosin 7a CTBP2 examine hair synaptic ribbons. The accumulation reactive oxygen species (ROS) was measured by 4‐HNE staining. gene expression changes cochlea analyzed using RNA sequencing. Results reduced levels ROS cochlear attenuated cell death caused hydrogen peroxide both HEI‐OC1 cells. In C57BL/6 mice, generation tumor necrosis factor‐α induced noise exposure, thereby protecting outer inner ribbons from damage through a mechanism involving PINK1/Parkin signaling pathway. preventive eliminated mitophagy inhibition. Conclusion VDAC1 inhibition enhances cells, playing critical role defending against oxidative stress inflammation. Downregulation may thus be considered therapeutic strategy for preventing reducing NIHL.

Язык: Английский

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Selenomethionine suppresses lung tumor growth without hepatorenal toxicity in mice via the induction of apoptosis-ferroptosis and angiogenesis inhibition

Tissue and Cell, Год журнала: 2025, Номер 96, С. 102956 - 102956

Опубликована: Май 10, 2025

Язык: Английский

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