Recent advances in small-molecule fluorescent probes for studying ferroptosis

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(18), P. 7752 - 7778

Published: Jan. 1, 2022

Ferroptosis is an iron-dependent, non-apoptotic form of programmed cell death driven by excessive lipid peroxidation (LPO). Mounting evidence suggests that the unique modality involved in development and progression several diseases including cancer, cardiovascular (CVDs), neurodegenerative disorders, etc. However, pathogenesis signalling pathways ferroptosis are not fully understood, possibly due to lack robust tools for highly selective sensitive imaging analytes complex living systems. Up now, various small-molecule fluorescent probes have been applied as promising chemosensors studying through tracking biomolecules or microenvironment-related parameters vitro vivo. In this review, we comprehensively reviewed recent ferroptosis, with a focus on analytes, design strategies bioimaging applications. We also provided new insights overcome major challenges emerging field.

Language: Английский

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

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 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

Language: Английский

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Iron Metabolism in Cardiovascular Disease: Physiology, Mechanisms, and Therapeutic Targets

Circulation Research, Journal Year: 2023, Volume and Issue: 132(3), P. 379 - 396

Published: Feb. 2, 2023

The cardiovascular system requires iron to maintain its high energy demands and metabolic activity. Iron plays a critical role in oxygen transport storage, mitochondrial function, enzyme However, excess is also cardiotoxic due ability catalyze the formation of reactive species promote oxidative damage. While mammalian cells have several redundant import mechanisms, they are equipped with single iron-exporting protein, which makes particularly sensitive overload. As result, levels tightly regulated at many homeostasis. dysregulation ranges from deficiency overload seen types disease, including heart failure, myocardial infarction, anthracycline-induced cardiotoxicity, Friedreich's ataxia. Recently, use intravenous therapy has been advocated patients failure certain criteria for deficiency. Here, we provide an overview systemic cellular homeostasis context physiology, deficiency, current therapeutic strategies, future perspectives.

Language: Английский

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The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 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.

Language: Английский

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

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 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

Language: Английский

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Hydrogen sulfide protects cardiomyocytes from doxorubicin-induced ferroptosis through the SLC7A11/GSH/GPx4 pathway by Keap1 S-sulfhydration and Nrf2 activation

Redox Biology, Journal Year: 2024, Volume and Issue: 70, P. 103066 - 103066

Published: Jan. 29, 2024

Recent studies have demonstrated that ferroptosis, a novel form of nonapoptotic regulated cell death plays an important role in doxorubicin (DOX)-induced cardiotoxicity (DoIC). Hydrogen sulfide (H

Language: Английский

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STAT3 signaling promotes cardiac injury by upregulating NCOA4-mediated ferritinophagy and ferroptosis in high-fat-diet fed mice

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 201, P. 111 - 125

Published: March 20, 2023

High-fat diet (HFD) intake provokes obesity and cardiac anomalies. Recent studies have found that ferroptosis plays a role in HFD-induced injury, but the underlying mechanism is largely unclear. Ferritinophagy an important part of regulated by nuclear receptor coactivator 4 (NCOA4). However, relationship between ferritinophagy damage has not been explored. In this study, we oleic acid/palmitic acid (OA/PA) increased level ferroptotic events including iron ROS accumulation, upregulation PTGS2 mRNA protein levels, reduced SOD GSH significant mitochondrial H9C2 cells, which could be reversed inhibitor ferrostatin-1 (Fer-1). Intriguingly, autophagy 3-methyladenine mitigated OA/PA-induced ferritin downregulation, overload ferroptosis. OA/PA NCOA4. Knockdown NCOA4 SiRNA partly reduction ferritin, lipid peroxidation, subsequently alleviated cell death, indicating NCOA4-mediated was required for Furthermore, demonstrated IL-6/STAT3 signaling. Inhibition or knockdown STAT3 effectively levels to protect cells from ferritinophagy-mediated ferroptosis, whereas overexpression plasmid appeared increase expression contribute classical events. Consistently, phosphorylated upregulation, activation, induction also occurred HFD-fed mice were responsible injury. addition, evidence piperlongumine, natural compound, cardiomyocytes both vitro vivo. Based on these findings, concluded one critical mechanisms contributing The STAT3/NCOA4/FTH1 axis might novel therapeutic target treatment

Language: Английский

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Ferroptosis‐modulating small molecules for targeting drug‐resistant cancer: Challenges and opportunities in manipulating redox signaling

Medicinal Research Reviews, Journal Year: 2023, Volume and Issue: 43(3), P. 614 - 682

Published: Jan. 19, 2023

Abstract Ferroptosis is an iron‐dependent cell death program that characterized by excessive lipid peroxidation. Triggering ferroptosis has been proposed as a promising strategy to fight cancer and overcome drug resistance in antitumor therapy. Understanding the molecular interactions structural features of ferroptosis‐inducing compounds might therefore open door efficient pharmacological strategies against aggressive, metastatic, therapy‐resistant cancer. We here summarize mechanisms requirements small molecules target central players ferroptosis. Focus placed on (i) glutathione peroxidase (GPX) 4, only GPX isoenzyme detoxifies complex membrane‐bound hydroperoxides, (ii) cystine/glutamate antiporter system X c − for regeneration, (iii) redox‐protective transcription factor nuclear erythroid 2‐related (NRF2), (iv) GPX4 repression combination with induced heme degradation via oxygenase‐1. deduce common ferroptotic activity highlight challenges development. Moreover, we critically discuss potential natural products lead structures provide comprehensive overview structurally diverse biogenic bioinspired trigger iron oxidation, inhibition thioredoxin/thioredoxin reductase or less defined modes action.

Language: Английский

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WGX50 mitigates doxorubicin-induced cardiotoxicity through inhibition of mitochondrial ROS and ferroptosis

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 17, 2023

Abstract Background Doxorubicin (DOX)-induced cardiotoxicity (DIC) is a major impediment to its clinical application. It indispensable explore alternative treatment molecules or drugs for mitigating DIC. WGX50, an organic extract derived from Zanthoxylum bungeanum Maxim, has anti-inflammatory and antioxidant biological activity, however, function mechanism in DIC remain unclear. Methods We established DOX-induced models both vitro vivo. Echocardiography histological analyses were used determine the severity of cardiac injury mice. The myocardial damage markers cTnT, CK-MB, ANP, BNP, ferroptosis associated indicators Fe 2+ , MDA, GPX4 measured using ELISA, RT-qPCR, western blot assays. morphology mitochondria was investigated with transmission electron microscope. levels mitochondrial membrane potential, ROS, lipid ROS detected JC-1, MitoSOX™, C11-BODIPY 581/591 probes. Results Our findings demonstrate that WGX50 protects via restraining ferroptosis. In vivo, effectively relieves doxorubicin-induced dysfunction, injury, fibrosis, damage, redox imbalance. vitro, preserves by reducing level potential increasing ATP production. Furthermore, reduces iron accumulation increases expression, regulates metabolism inhibit Conclusion Taken together, pathway, which provides novel insights as promising drug candidate cardioprotection. Graphic abstract

Language: Английский

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Ferroptosis in mitochondrial cardiomyopathy

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 34(2), P. 150 - 160

Published: July 5, 2023

Language: Английский

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