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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The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Год журнала: 2023, Номер 4(1)

Опубликована: Окт. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Язык: Английский

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Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Язык: Английский

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The molecular mechanisms and potential drug targets of ferroptosis in myocardial ischemia–reperfusion injury

Life Sciences, Год журнала: 2024, Номер 340, С. 122439 - 122439

Опубликована: Янв. 24, 2024

Myocardial ischemia–reperfusion injury (MIRI), caused by the initial interruption and subsequent restoration of coronary artery blood, results in further damage to cardiac function, affecting prognosis patients with acute myocardial infarction. Ferroptosis is an iron-dependent, superoxide-driven, non-apoptotic form regulated cell death that involved pathogenesis MIRI. characterized accumulation lipid peroxides (LOOH) redox disequilibrium. Free iron ions can induce oxidative stress as a substrate Fenton reaction lipoxygenase (LOX) participate inactivation variety antioxidants including CoQ10 GPX4, destroying balance causing death. The metabolism amino acid, iron, lipids, associated pathways, considered specific hallmark ferroptosis. This review systematically summarizes latest research progress on mechanisms ferroptosis discusses analyzes therapeutic approaches targeting alleviate

Язык: Английский

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Ferroptosis, a Regulated Form of Cell Death, as a Target for the Development of Novel Drugs Preventing Ischemia/Reperfusion of Cardiac Injury, Cardiomyopathy and Stress-Induced Cardiac Injury

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 897 - 897

Опубликована: Янв. 11, 2024

The hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is about 6% and has not decreased recent years. leading cause of death these ischemia/reperfusion (I/R) cardiac injury. It quite obvious that there an urgent need to create new drugs for the treatment STEMI based on knowledge pathogenesis I/R injury, particular, molecular mechanism ferroptosis. In this study, it was demonstrated ferroptosis involved development antitumor drug-induced cardiomyopathy, diabetic septic inflammation. There indirect evidence participates stress-induced activation AMPK, PKC, ERK1/2, PI3K, Akt prevents inhibition HO-1 alleviates roles GSK-3β NOS regulation require further study. stimulation Nrf2, STAT3 TLR4 NF-κB promotes cardiomyocytes. MiR-450b-5p miR-210-3p can increase tolerance cardiomyocytes hypoxia/reoxygenation through Circ_0091761 RNA, miR-214-3p, miR-199a-5p, miR-208a/b, miR-375-3p, miR-26b-5p miR-15a-5p aggravate

Язык: Английский

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Dexmedetomidine Ameliorates Myocardial Ischemia‐Reperfusion Injury by Inhibiting MDH2 Lactylation via Regulating Metabolic Reprogramming

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Окт. 28, 2024

Abstract Myocardial ischemia‐reperfusion injury (MIRI) significantly worsens the outcomes of patients with cardiovascular diseases. Dexmedetomidine (Dex) is recognized for its cardioprotective properties, but related mechanisms, especially regarding metabolic reprogramming, have not been fully clarified. A total 60 heart valve disease are randomly assigned to Dex or control group. Blood samples collected analyze cardiac biomarkers and metabolomics. In vivo vitro rat models MIRI utilized assess effects on function, lactate production, mitochondrial function. It found that postoperative CK‐MB cTNT levels lower in Metabolomics reveals regulates reprogramming reduces level. Dex‐treated rats, myocardial infarction area reduced, contractility improved. inhibits glycolysis, lactate, improves function following MIRI. Lactylation proteomics identifies lactylation Malate Dehydrogenase 2（MDH2), thus alleviating injury. Further studies reveal MDH2 induces ferroptosis, leading by impairing Mechanistic analyses upregulates Nuclear Receptor Subfamily 3 Group C Member 1（NR3C1) phosphorylation, downregulates Pyruvate Kinase 4 (PDK4), production lactylation. These findings provide new therapeutic targets mechanisms treatment

Язык: Английский

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Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis

Redox Biology, Год журнала: 2024, Номер 76, С. 103321 - 103321

Опубликована: Авг. 19, 2024

Cell death constitutes a critical component of the pathophysiology cardiovascular diseases. A growing array non-apoptotic forms regulated cell (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified is intimately linked to various conditions. These RCD are governed by genetically programmed mechanisms within cell, with epigenetic modifications being common crucial regulatory method. Such include DNA methylation, RNA histone acetylation, non-coding RNAs. This review recaps roles modifications, RNAs in diseases, well which regulate key proteins involved death. Furthermore, we systematically catalog existing pharmacological agents targeting novel their action article aims underscore pivotal role precisely regulating specific pathways thus offering potential new therapeutic avenues that may prove more effective safer than traditional treatments.

Язык: Английский

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Sialylation on vesicular integrin β1 determined endocytic entry of small extracellular vesicles into recipient cells

Cellular & Molecular Biology Letters, Год журнала: 2024, Номер 29(1)

Опубликована: Апрель 1, 2024

Abstract Background Small extracellular vesicles (sEV) are closely associated with the development and metastasis of many types mammalian cancer. Glycoconjugates highly expressed on sEV play important roles in biogenesis their interaction other cells. However, study vesicular glycoconjugates far behind proteins nucleic acids. Especially, functions sialic acids which terminal components glycoconjugates, poorly understood sEV. Methods Sialic acid levels from plasma bladder cancer cells were determined by ELISA lectin blotting. Effects sialylation uptake flow cytometry. Vesicular glycoproteins bearing responsible for was identified proteomics density gradient centrifugation, site-specific assayed N -glycosylation site mutation. integrin β1 pro-metastatic function vivo explored using Balb/c nu/nu mice. Results (1) Increased observed malignant (2) Elimination impaired recipient (3) to a key role uptake. (4) Desialylation hybrid domain inhibited its binding matrix fibronectin, reduced entry into (5) Sialylation affected Conclusions Taken together, our findings indicate functional reprogramming plasticity surrounding normal epithelial Graphical

Язык: Английский

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Extracellular vesicles in cardiovascular diseases: From pathophysiology to diagnosis and therapy

Cytokine & Growth Factor Reviews, Год журнала: 2023, Номер 74, С. 40 - 55

Опубликована: Сен. 28, 2023

Язык: Английский

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Metabolite itaconate in host immunoregulation and defense

Cellular & Molecular Biology Letters, Год журнала: 2023, Номер 28(1)

Опубликована: Дек. 2, 2023

Metabolic states greatly influence functioning and differentiation of immune cells. Regulating the metabolism cells can effectively modulate host response. Itaconate, an intermediate metabolite derived from tricarboxylic acid (TCA) cycle cells, is produced through decarboxylation cis-aconitate by decarboxylase in mitochondria. The gene encoding known as response 1 (IRG1). In to external proinflammatory stimulation, macrophages exhibit high IRG1 expression. IRG1/itaconate inhibits succinate dehydrogenase activity, thus influencing metabolic status macrophages. Therefore, itaconate serves a link between macrophage metabolism, oxidative stress, response, ultimately regulating function. Studies have demonstrated that acts on various signaling pathways, including Keap1-nuclear factor E2-related 2-ARE ATF3-IκBζ axis, stimulator interferon genes (STING) pathway exert antiinflammatory antioxidant effects. Furthermore, several studies reported affects cancer occurrence development diverse pathways. this paper, we provide comprehensive review role its derivatives regulation functions. By furthering our understanding itaconate, intend shed light potential for treating inflammatory diseases offer new insights field.

Язык: Английский

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