Recent progress in ferroptosis: inducers and inhibitors

Cell Death Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: Dec. 29, 2022

Ferroptosis is a new iron-dependent form of programmed cell death characterized by iron accumulation and lipid peroxidation. In recent years, ferroptosis has garnered enormous interest in disease treatment research communities pursuit to reveal the mechanism key targets because closely related pathophysiological processes many diseases. Recent studies have shown some targets, such as glutathione peroxidase 4 (GPX4) System Xc-, several inducers inhibitors been developed regulate these targets. With emergence on made developments. The selection use are very important for work. This paper briefly introduces regulatory metabolic pathway, lists categorizes commonly used recently inhibitors, discusses their medical application. ends with potential future direction ferroptosis.

Language: Английский

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Targeting ferroptosis in acute kidney injury

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(2)

Published: Feb. 24, 2022

Acute kidney injury (AKI) is a major public health problem with high incidence and mortality. As form of programmed cell death (PCD), ferroptosis could be considered as process iron accumulation enhanced lipid peroxidation. Recently, the fundamental roles in AKI have attracted much attention. The network mechanism its to chronic disease (CKD) transition complicated multifactorial. Strategies targeting show great potential. Here, we review research progress on participation AKI. We hope that this work will provide clues for further studies

Language: Английский

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Ferroptosis is involved in deoxynivalenol-induced intestinal damage in pigs

Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 16, 2023

Deoxynivalenol (DON) is a widespread issue for feed and food safety, leading to animal human health risks. The objective of this study was determine whether ferroptosis involved in DON-induced intestinal injury piglets. Three groups 21-day-old male weanling piglets (n = 7/group) were fed control diet, or diet adding 1.0 3.0 mg DON/kg. At week 4, serum small intestines collected assay biochemistry, histology, redox status ferroptosis-related genes expression. In addition, the involvement role FTL gene cell death further verified IPEC-J2 cells.Compared control, dietary supplementation DON at mg/kg induced different degrees damage duodenum, jejunum ileum, increased (P < 0.05) lipopolysaccharide concentration by 46.2%-51.4%. Dietary (or) concentrations malondialdehyde (17.4%-86.5%) protein carbonyl 33.1%-92.3% ileum. supplemented with upregulated ferroptotic (DMT1) anti-ferroptotic (FTL FTH1), while downregulated (FPN, FSP1 CISD1) duodenum porcine. Furthermore, vitro has demonstrated that deferiprone, potent inhibitor, mitigated cytotoxicity porcine cells. Additionally, deferiprone prevented alleviated dysregulation (ACSL4 FTL) Moreover, specific siRNA knockdown expression compromised cells.In conclusion, revealed porcine, sheds new light on toxicity

Language: Английский

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Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 647 - 647

Published: Feb. 2, 2024

Copper, an essential element for various biological processes, demands precise regulation to avert detrimental health effects and potential cell toxicity. This paper explores the mechanisms of copper-induced death, known as cuproptosis, its disease implications, including cancer therapy. Copper ionophores, such elesclomol disulfiram, increase intracellular copper levels. elevation triggers oxidative stress subsequent offering implications in Additionally, ionophores disrupt mitochondrial respiration protein lipoylation, further contributing toxicity death. Potential targets biomarkers are identified, can be targeted those proteins trigger cuproptosis. The role different cancers is discussed understand therapies using nanomaterials, chelators. Furthermore, explored through diseases Wilson Menkes physiological copper. Exploring cuproptosis presents opportunity improve treatments copper-related disorders cancers, with bring significant advancements modern medicine.

Language: Английский

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Progress and Challenges in Tumor Ferroptosis Treatment Strategies: A Comprehensive Review of Metal Complexes and Nanomedicine

Small, Journal Year: 2024, Volume and Issue: 20(25)

Published: Jan. 14, 2024

Abstract Ferroptosis is a new form of regulated cell death featuring iron‐dependent lipid peroxides accumulation to kill tumor cells. A growing body evidence has shown the potential ferroptosis‐based cancer therapy in eradicating refractory malignancies that are resistant apoptosis‐based conventional therapies. In recent years, studies have reported number ferroptosis inducers can increase vulnerability cells by regulating ferroptosis‐related signaling pathways. Encouraged rapid development ferroptosis‐driven therapies, interdisciplinary fields combine ferroptosis, pharmaceutical chemistry, and nanotechnology focused. First, prerequisites metabolic pathways for briefly introduced. Then, detail emerging designed boost ferroptosis‐induced therapy, including metal complexes, metal‐based nanoparticles, metal‐free nanoparticles summarized. Subsequently, application synergistic strategies with apoptosis other emphasis on use both cuproptosis induce redox dysregulation intracellular bimetallic copper/iron metabolism disorders during treatment discussed. Finally, challenges associated clinical translation future directions potentiating therapies highlighted.

Language: Английский

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Immunogenicity of ferroptosis in cancer: a matter of context?

Trends in cancer, Journal Year: 2024, Volume and Issue: 10(5), P. 407 - 416

Published: Feb. 16, 2024

Language: Английский

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Copper ions induces ferroptosis in Staphylococcus aureus and promotes healing of MRSA-induced wound infections

Microbiological Research, Journal Year: 2025, Volume and Issue: 296, P. 128122 - 128122

Published: Feb. 26, 2025

Language: Английский

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Dysregulation of Iron Homeostasis in the Central Nervous System and the Role of Ferroptosis in Neurodegenerative Disorders

Antioxidants and Redox Signaling, Journal Year: 2021, Volume and Issue: 37(1-3), P. 150 - 170

Published: Sept. 26, 2021

Significance: Iron accumulation occurs in the central nervous system (CNS) a variety of neurological conditions as diverse spinal cord injury, stroke, multiple sclerosis, Parkinson's disease, and others. is redox-active metal that gives rise to damaging free radicals if its intracellular levels are not controlled or it properly sequestered within cells. The iron due dysregulation mechanisms control cellular homeostasis. Recent Advances: molecular regulate homeostasis have been revealed much detail past three decades, new advances continue be made. Understanding which aspects dysregulated different will provide insights into causes iron-mediated tissue damage. iron-dependent lipid peroxidation leading cell death, called ferroptosis, has provided useful highly relevant for lipid-rich environment CNS. Critical Issues: This review examines normal homeostasis, these disorders, more recent work on how can induce damage via ferroptosis. Future Directions: Quick reliable tests needed determine when ferroptosis contributes pathogenesis disorders. In addition, there need develop better druggable agents scavenge reduce CNS currently few effective treatments. Antioxid. Redox Signal. 37, 150-170.

Language: Английский

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Ferroportin-dependent ferroptosis induced by ellagic acid retards liver fibrosis by impairing the SNARE complexes formation

Redox Biology, Journal Year: 2022, Volume and Issue: 56, P. 102435 - 102435

Published: Aug. 23, 2022

Chronic liver injury causing fibrosis is a major cause of morbidity and mortality worldwide. Targeting the suppression hepatic stellate cell (HSC) activation recognized as an effective strategy for treatment fibrosis. Ellagic acid (EA), natural polyphenol product isolated from fruits vegetables, possesses many biological functions. Here, EA exerts its antifibrotic activity by inducing ferroptotic death activated HSCs, which accompanied redox-active iron accumulation, lipid peroxidation, GSH depletion in CCl4 mice human LX-2 cells. The specific ferroptosis inhibitor ferrostatin-1 prevented EA-induced death. Mechanistically, impairs formation vesicle-associated membrane protein 2 (VAMP2)/syntaxin 4 VAMP2/synaptosome-associated 23 complexes suppressing VAMP2 expression enhancing degradation proteasome-dependent pathway. This leads to impairment ferroportin (FPN, exporter) translocation intracellular extrusion. Interestingly, overexpression inhibits role blocking FPN increasing ferritin content (an storage marker). In contrast, knockdown shows synergistic effect on EA-mediated events both HSCs. Additionally, HSC-specific impaired HSC mouse fibrosis, increased inhibitory Taken together, our data suggest that effects FPN-dependent HSCs disrupting SNARE complexes, will hopefully serve prospective compound treatment.

Language: Английский

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Ferroptosis inhibitor ferrostatin‑1 alleviates homocysteine‑induced ovarian granulosa cell injury by regulating TET activity and DNA methylation

Molecular Medicine Reports, Journal Year: 2022, Volume and Issue: 25(4)

Published: Feb. 15, 2022

Polycystic ovary syndrome is one of the most common endocrine and metabolic gynecological disorders, which dysfunction ovarian granulosa cells a key contributing factor. The aim present study was to explore role ferrostatin‑1 (Fer‑1), ferroptosis inhibitor, in cell injury model established by homocysteine (Hcy)‑induced KGN line potential underlying mechanism. Cell viability measured using Counting Kit‑8 assay presence or absence Hcy Fer‑1. apoptosis assessed TUNEL staining expression levels apoptosis‑related proteins were western blotting. To effects Fer‑1 on oxidative stress Hcy‑treated cells, reactive oxygen species (ROS), malondialdehyde (MDA), lactate dehydrogenase (LDH) glutathione (GSH) their corresponding kits. Furthermore, Fe2+ Phen Green™ SK labeling blotting performed measure protein ferroptosis‑associated GPX4, SLC7A11, ASCL4 DMT1. Subsequently, DNA methylation ten‑eleven translocation (TET) 1/2 demethylase also detected evaluate extent overall after treatment. TET1/2 inhibitor Bobcat339 hydrochloride applied treat before evaluating possible methylation. found markedly elevate following rate Fer‑1‑treated groups decreased, accompanied downregulated Bax cleaved caspase‑3 upregulated Bcl‑2 expression. In addition, treatment reduced ROS, MDA LDH whilst enhancing GSH. significantly decreased treatment, elevated peroxidase 4 reducing solute carrier family 7 member 11, achaete‑scute BHLH transcription factor divalent metal transporter 1 inhibited enhanced levels, reversed with hydrochloride. Subsequent experiments viability, stress, content, ferroptosis‑ revealed that Hcy‑induced injury. These results suggest may potentially protect against increasing TET

Language: Английский

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