Nox4-and Tf/TfR-mediated peroxidation and iron overload exacerbate neuronal ferroptosis after intracerebral hemorrhage: Involvement of EAAT3 dysfunction

Xie, Jiayu; Lv, Hongzhu; Liu, Xuanbei; Xia, Zhennan; Li, Jiangwei; Hong, Enhui; Ding, Boyun; Zhang, Wenying; Chen, Yizhao

doi:10.1016/j.freeradbiomed.2023.02.015

Cited by 20 publications

(12 citation statements)

References 58 publications

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“…[ 328 ] NOX4‐mediated peroxidation and Tf/TfR‐mediated iron overload exacerbate neuronal ferroptosis in a rat model of ICH. [ 320 ] In addition, astrocyte‐derived glutamine synthesis was increased in ICH rats, while neuronal cysteine uptake was diminished, evidenced by downregulation of EAAT3 and GPX4 expression. Inhibiting NOX4 and iron chelation partially restored neuronal levels of EAAT3 and GPX4 expression and inhibited neuronal ferroptosis, suggesting that inhibition of these pathological signals can protect the hemorrhagic brain.…”

Section: Ferroptosis In Neurological Diseasesmentioning

confidence: 99%

“…Inhibiting NOX4 and iron chelation partially restored neuronal levels of EAAT3 and GPX4 expression and inhibited neuronal ferroptosis, suggesting that inhibition of these pathological signals can protect the hemorrhagic brain. [ 320 ] Increased methyltransferase‐like 3, a N 6 ‐methyladenosine (m 6 A) methyltransferases (“writers”) promoted secondary brain injury after ICH by inhibiting GPX4 expression in an m 6 A‐dependent manner. [ 329 ] These results implied that m 6 A‐dependent epigenetic modification of GPX4 is involved in the genesis of secondary brain injury after ICH.…”

Section: Ferroptosis In Neurological Diseasesmentioning

confidence: 99%

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Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes

Wang

et al. 2023

Advanced Science

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Emerging evidence suggests that ferroptosis, a unique regulated cell death modality that is morphologically and mechanistically different from other forms of cell death, plays a vital role in the pathophysiological process of neurodegenerative diseases, and strokes. Accumulating evidence supports ferroptosis as a critical factor of neurodegenerative diseases and strokes, and pharmacological inhibition of ferroptosis as a therapeutic target for these diseases. In this review article, the core mechanisms of ferroptosis are overviewed and the roles of ferroptosis in neurodegenerative diseases and strokes are described. Finally, the emerging findings in treating neurodegenerative diseases and strokes through pharmacological inhibition of ferroptosis are described. This review demonstrates that pharmacological inhibition of ferroptosis by bioactive small‐molecule compounds (ferroptosis inhibitors) could be effective for treatments of these diseases, and highlights a potential promising therapeutic avenue that could be used to prevent neurodegenerative diseases and strokes. This review article will shed light on developing novel therapeutic regimens by pharmacological inhibition of ferroptosis to slow down the progression of these diseases in the future.

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Section: Ferroptosis In Neurological Diseasesmentioning

confidence: 99%

Section: Ferroptosis In Neurological Diseasesmentioning

confidence: 99%

Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes

Wang

et al. 2023

Advanced Science

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“…It has been reported that transferrin receptor 1 (TFR1) (Xie et al, 2023), six-transmembrane epithelial antigen of the prostate whose dysregulation makes cells more sensitive to ferroptosis by increasing intracellular iron levels. In the case of NCOA4, high intraocular pressure induces ferroptosis in retinal ganglion cells by promoting NCOA4-mediated ferritin degradation, which leads to permanent vision damage during glaucoma (F. Yao et al, 2023).…”

Section: Overview Of Ferroptosismentioning

confidence: 99%

“…At the cellular level, all aspects of iron metabolism, such as absorption, storage, utilization, and export, work in concert to maintain iron homeostasis (Roemhild et al, 2021). It has been reported that transferrin receptor 1 (TFR1) (Xie et al, 2023), six‐transmembrane epithelial antigen of the prostate 3 (STEAP3) (Wu et al, 2022), divalent metal transporter 1 (DMT1) (Shi, Xue, et al, 2023), nuclear receptor coactivator 4 (NCOA4) (Y. H. Tang, Wu, et al, 2023), and heme oxygenase 1 (HO‐1) (Shi, Wang, et al, 2023) are the key players involved in iron metabolism, whose dysregulation makes cells more sensitive to ferroptosis by increasing intracellular iron levels. In the case of NCOA4, high intraocular pressure induces ferroptosis in retinal ganglion cells by promoting NCOA4‐mediated ferritin degradation, which leads to permanent vision damage during glaucoma (F. Yao et al, 2023).…”

Section: Overview Of Ferroptosismentioning

confidence: 99%

Ferroptosis: Potential opportunities for natural products in cancer therapy

Nie,

Shen,

Zhou

et al. 2023

Phytotherapy Research

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Cancer cells often exhibit defects in the execution of cell death, resulting in poor clinical outcomes for patients with many cancer types. Ferroptosis is a newly discovered form of programmed cell death characterized by intracellular iron overload and lipid peroxidation in the cell membrane. Increasing evidence suggests that ferroptosis is closely associated with a wide variety of physiological and pathological processes, particularly in cancer. Notably, various bioactive natural products have been shown to induce the initiation and execution of ferroptosis in cancer cells, thereby exerting anticancer effects. In this review, we summarize the core regulatory mechanisms of ferroptosis and the multifaceted roles of ferroptosis in cancer. Importantly, we focus on natural products that regulate ferroptosis in cancer cells, such as terpenoids, polyphenols, alkaloids, steroids, quinones, and polysaccharides. The clinical efficacy, adverse effects, and drug–drug interactions of these natural products need to be evaluated in further high‐quality studies to accelerate their application in cancer treatment.

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“…Extensive research has been conducted on ferroptosis, which is involved in cell metabolism, oxidative and electrophilic stress responses, and immune responses [17][18][19]. Recently, ferroptosis has been linked to many degenerative diseases, including brain injury, cerebral hemorrhage, Alzheimer's disease, cancer, stroke, and others [20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

4-Octyl itaconate protects chondrocytes against IL-1β-induced oxidative stress and ferroptosis by inhibiting GPX4 methylation in osteoarthritis

Pan

Kong

et al. 2023

Preprint

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The role of oxidative stress and ferroptosis in the pathogenesis of osteoarthritis (OA) is significant. 4-Octyl Itaconate (OI) has been shown to have protective effects against oxidative stress and inflammatory response, and has been identified as a potential therapeutic agent for OA. However, the specific effects of OI on the regulation of chondrocyte degeneration, oxidative stress, and ferroptosis require further investigation. The objective of our study was to examine the effects of OI on IL-1β-induced chondrocytes and an OA mouse model. Our results demonstrate that OI effectively mitigates IL-1β-induced chondrocyte degeneration in a dose-dependent manner. Additionally, OI exhibited a significant inhibitory effect on ROS production and mitigated the decline in Recombinant Glutathione Peroxidase 4 (GPX4) levels induced by IL-1β and Erastin, a ferroptosis activator. As a result, OI demonstrated potential in attenuating the degenerative effects of IL-1β and Erastin on chondrocytes, possibly through the reduction of ferroptosis. The molecular mechanism underlying OI's regulation of GPX4 expression in chondrocytes was found to involve the repression of GPX4 methylation. Furthermore, the inhibition of GPX4 methylation was observed to improve IL-1β-triggered degeneration, oxidative stress, and ferroptosis in chondrocytes. Comparable outcomes were obtained in animal models of osteoarthritis (OA). The utilization of OI and Ferrostatin-1 (Fer-1) mitigated the progression of OA and cartilage degeneration in the mouse model of OA, which was established by destabilization of medial meniscus (DMM). Consequently, it can be inferred that OI alleviates degeneration, oxidative stress, and ferroptosis in IL-1β-treated chondrocytes by inhibiting GPX4 methylation both in vitro and in vivo. These findings indicate that OI represents a promising new therapeutic modality for OA.

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Nox4-and Tf/TfR-mediated peroxidation and iron overload exacerbate neuronal ferroptosis after intracerebral hemorrhage: Involvement of EAAT3 dysfunction

Cited by 20 publications

References 58 publications

Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes

Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes

Ferroptosis: Potential opportunities for natural products in cancer therapy

4-Octyl itaconate protects chondrocytes against IL-1β-induced oxidative stress and ferroptosis by inhibiting GPX4 methylation in osteoarthritis

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