Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Дек. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Язык: Английский

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An integrated view of lipid metabolism in ferroptosis revisited via lipidomic analysis

Experimental & Molecular Medicine, Год журнала: 2023, Номер 55(8), С. 1620 - 1631

Опубликована: Авг. 23, 2023

Abstract Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. This process contributes to cellular and tissue damage in various human diseases, such as cardiovascular neurodegeneration, liver disease, cancer. Although polyunsaturated fatty acids (PUFAs) membrane phospholipids are preferentially oxidized, saturated/monounsaturated (SFAs/MUFAs) also influence peroxidation ferroptosis. In this review, we first explain how cells differentially synthesize SFA/MUFAs PUFAs they control acid pools via uptake β-oxidation, impacting Furthermore, discuss stored different lipids, diacyl or ether with head groups; triglycerides; cholesterols. Moreover, these released from molecules. summary, provide an integrated view the diverse dynamic metabolic processes context ferroptosis revisiting lipidomic studies. Thus, review development therapeutic strategies for ferroptosis-related diseases.

Язык: Английский

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STING promotes ferroptosis through NCOA4-dependent ferritinophagy in acute kidney injury

Free Radical Biology and Medicine, Год журнала: 2023, Номер 208, С. 348 - 360

Опубликована: Авг. 26, 2023

Ferroptosis in tubules has been implicated the pathogenesis of acute kidney injury (AKI), whereas regulatory mechanism remains unclear. The stimulator interferon genes (STING) is previously recognized as a critical mediator innate immunity via DNA-sensing pathway and increasingly linked to lipid peroxidation, hallmark ferroptosis. Herein we investigated role underlying STING AKI models established by ischemia/reperfusion (IR) C57BL mice. expression level was predominantly increased after IR treatment. Besides, deficiency markedly alleviated IR-induced tissue damage renal dysfunction. Consistently, vitro experiments demonstrated that increase ferroptotic cell death, ROS production decrease GSH peroxidase 4 (GPX4) tubular cells subjected ferroptosis agonist or hypoxia/reoxygenation intervention were all mitigated genetic pharmacological inhibition STING, while exacerbated overexpression. Further, these detrimental effects overexpression relied on induction ferritinophagy, i.e. autophagic degradation ferritin, leading iron overload. Mechanistically, mediated initiation ferritinophagy through interacting with nuclear receptor coactivator (NCOA4), fundamental for transfer ferritin into lysosome. Collectively, contributes during ischemic facilitating NCOA4-mediated shows potential promising therapeutic choice AKI.

Язык: Английский

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Amino acid metabolism disorder and oxidative stress took part in EGCG alleviating Mn-caused ferroptosis via miR-9-5p/got1 axis

Journal of Hazardous Materials, Год журнала: 2025, Номер 489, С. 137656 - 137656

Опубликована: Фев. 21, 2025

Язык: Английский

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Ferroptosis: The Entanglement between Traditional Drugs and Nanodrugs in Tumor Therapy

Advanced Healthcare Materials, Год журнала: 2023, Номер 12(12)

Опубликована: Янв. 19, 2023

Ferroptosis is a non-apoptotic programmed cell death caused by the accumulation of lipid peroxide. System Xc-/glutathione peroxidase 4 (GPX4) axis and iron are two main pathways regulating ferroptosis. Simultaneously, multiple also involved in ferroptosis regulation. an intense area current study. With improvement regulatory mechanisms that underlie ferroptosis, variety drugs associated with have been discovered developed for cancer therapy. Among them, traditional were initially. Small molecule compounds regulate signaling pathway complexes promote Fenton reaction become important inducing In recent years, emerging development nanotechnology has promoted research nanodrugs. Iron-based nanomaterials extensively tested as ferroptosis-inducing agents. Furthermore, nanoscale drug delivery systems offer suitable scaffold therapies. Traditional nanodrugs complementary, each their own strengths limitations. This review describes latest studies on regulation tumor cells focuses entanglement between To conclude, challenges perspectives this field put forward.

Язык: Английский

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Broadening horizons: the multifaceted functions of ferroptosis in kidney diseases

International Journal of Biological Sciences, Год журнала: 2023, Номер 19(12), С. 3726 - 3743

Опубликована: Янв. 1, 2023

Ferroptosis is an iron-dependent programmed cell death pattern that characterized by iron overload, reactive oxygen species (ROS) accumulation and lipid peroxidation. Growing viewpoints support the imbalance of homeostasis disturbance metabolism contribute to tissue or organ injury in various kidney diseases triggering ferroptosis. At present, key regulators complicated network mechanisms associated with ferroptosis have been deeply studied; however, its role initiation progression has not fully revealed. Herein, we aim discuss features, ferroptosis, explore emerging roles organelles gather pharmacological progress, systematically summarize most recent discoveries about crosstalk between diseases, including renal carcinoma (RCC), acute (AKI), diabetic disease (DKD), autosomal dominant polycystic (ADPKD), fibrosis, lupus nephritis (LN) IgA nephropathy. We further conclude potential therapeutic strategies targeting for prevention treatment hope this work will provide insight study pathogenesis kidney-related diseases.

Язык: Английский

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Acute kidney injury and distant organ dysfunction–network system analysis

Kidney International, Год журнала: 2023, Номер 103(6), С. 1041 - 1055

Опубликована: Апрель 7, 2023

Язык: Английский

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DMT1 differentially regulates mitochondrial complex activities to reduce glutathione loss and mitigate ferroptosis

Free Radical Biology and Medicine, Год журнала: 2023, Номер 207, С. 32 - 44

Опубликована: Июль 5, 2023

Mitochondria are vital for energy production and redox homeostasis, yet knowledge of relevant mechanisms remains limited. Here, through a genome-wide CRISPR-Cas9 knockout screening, we have identified DMT1 as major regulator mitochondria membrane potential. Our findings demonstrate that deficiency increases the activity mitochondrial complex I reduces III. Enhanced leads to increased NAD+ production, which activates IDH2 by promoting its deacetylation via SIRT3. This results in higher levels NADPH GSH, improve antioxidant capacity during Erastin-induced ferroptosis. Meanwhile, loss III impairs biogenesis promotes mitophagy, contributing suppression Thus, differentially regulates activities cooperatly suppress Furthermore, NMN, an alternative method increasing NAD+, exhibits similar protective effects against ferroptosis boosting GSH manner deficiency, shedding light on potential therapeutic strategy ferroptosis-related pathologies.

Язык: Английский

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Emerging significance and therapeutic targets of ferroptosis: a potential avenue for human kidney diseases

Cell Death and Disease, Год журнала: 2023, Номер 14(9)

Опубликована: Сен. 22, 2023

Abstract Kidney diseases remain one of the leading causes human death and have placed a heavy burden on medical system. Regulated cell contributes to pathology plethora renal diseases. Recently, with in-depth studies into kidney death, new iron-dependent modality, known as ferroptosis, has been identified attracted considerable attention among researchers in pathogenesis therapeutics treat them. The majority suggest that ferroptosis plays an important role pathologies multiple diseases, such acute injury (AKI), chronic disease, carcinoma. In this review, we summarize recently regulatory molecular mechanisms discuss pathways action various describe protective effect inhibitors against especially AKI. By summarizing prominent roles different progress made studying provide directions strategies for future research summary, ferroptotic factors are potential targets therapeutic intervention alleviate targeting them may lead treatments patients

Язык: Английский

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Cyanidin-3-glucoside inhibits ferroptosis in renal tubular cells after ischemia/reperfusion injury via the AMPK pathway

Molecular Medicine, Год журнала: 2023, Номер 29(1)

Опубликована: Апрель 3, 2023

Abstract Background Ferroptosis, which is characterized by lipid peroxidation and iron accumulation, closely associated with the pathogenesis of acute renal injury (AKI). Cyanidin-3-glucoside (C3G), a typical flavonoid that has anti-inflammatory antioxidant effects on ischemia‒reperfusion (I/R) injury, can induce AMP-activated protein kinase (AMPK) activation. This study aimed to show C3G exerts nephroprotective against I/R-AKI related ferroptosis regulating AMPK pathway. Methods Hypoxia/reoxygenation (H/R)-induced HK-2 cells mice were treated or without inhibiting AMPK. The level intracellular free iron, expression ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) glutathione peroxidase (GPX4), levels markers 4-hydroxynonenal (4-HNE), reactive oxygen species (ROS) malondialdehyde (MDA) examined. Results We observed inhibitory effect in vitro vivo, was reversion excessive decrease 4-HNE, ROS, MDA ACSL4 expression, an increase GPX4 (GSH) levels. Notably, inhibition CC significantly abrogated models vivo vitro. Conclusion Our results provide new insight into activating

Язык: Английский

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