Parkin inhibits iron overload-induced cardiomyocyte ferroptosis by ubiquitinating ACSL4 and modulating PUFA-phospholipids metabolism

Acta Pharmaceutica Sinica B, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Astaxanthin mitigates doxorubicin-induced cardiotoxicity via inhibiting ferroptosis and autophagy: a study based on bioinformatic analysis and in vivo/vitro experiments

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Янв. 21, 2025

Background Doxorubicin (DOX), a widely employed chemotherapeutic agent in cancer treatment, has seen restricted use recent years owing to its associated cardiotoxicity. Current reports indicate that doxorubicin-induced cardiotoxicity (DIC) is complex phenomenon involving various modes of cell death. Astaxanthin (ASX), natural carotenoid pigment, garnered significant attention for numerous health benefits. Recent studies have shown ASX broad and effective cardiovascular protective effect. Our study aims investigate the effects against DIC elucidate underlying mechanisms. This substantial practical significance clinical application DOX. Methods Bioinformatic analyses were conducted using transcriptomic data from gene expression omnibus (GEO) database identify key mechanisms DIC. Network pharmacology was predict potential pathways targets through which exerts on In vitro experiments, following pretreatment with ASX, H9C2 cells exposed Cell viability, injury protein levels ferroptosis autophagy assessed. animal rats underwent 4 weeks gavage treatment doses followed by intraperitoneal injections DOX every 2 days during final week. Histological, serum, evaluate Results The bioinformatics analysis revealed are closely development may exert an anti-DIC effect modulating autophagy. experimental results show significantly mitigates DOX-induced myocardial tissue damage, inflammatory response, oxidative stress, damage cells. Mechanistically, markedly ameliorates both vivo . Specifically, upregulates solute carrier family 7 member 11 (SLC7A11) glutathione peroxidase (GPX4), while downregulating transferrin receptor 1 (TFRC), ferritin heavy chain (FTH1) light (FTL). Additionally, enhances P62 decreases Beclin1 microtubule-associated proteins 3 (LC3). Conclusion critical factors influencing occurrence progression can alleviate inhibiting

Язык: Английский

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The role of ferroptosis in neurodegenerative diseases

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Окт. 15, 2024

Ferroptosis represents an iron − and lipid peroxidation (LPO)-mediated form of regulated cell death (RCD). Recent evidence strongly suggests the involvement ferroptosis in various neurodegenerative diseases (NDs), particularly Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), multiple sclerosis (MS), amyotrophic lateral (ALS), among others. The treatment poses both opportunities challenges context ND. This review provides a comprehensive overview characteristic features, induction inhibition ferroptosis, highlighting inhibitor underlying mechanisms responsible for its occurrence. Moreover, explores how these contribute to pathogenesis progression major disorders. Additionally, it presents novel insights into role ND summarizes recent advancements development therapeutic approaches targeting ferroptosis. These hold potential guide future strategies aimed at effectively managing debilitating medical conditions.

Язык: Английский

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1,25-D3 ameliorates ischemic brain injury by alleviating endoplasmic reticulum stress and ferroptosis: Involvement of vitamin D receptor and p53 signaling

Cellular Signalling, Год журнала: 2024, Номер 122, С. 111331 - 111331

Опубликована: Июль 31, 2024

Язык: Английский

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Aprocitentan mitigates doxorubicin-induced cardiotoxicity by inhibiting cuproptosis, oxidative stress, and mitochondrial impairments via the activation of sirtuin 7

International Immunopharmacology, Год журнала: 2025, Номер 148, С. 114141 - 114141

Опубликована: Янв. 28, 2025

Язык: Английский

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Application of Nanomaterial-Mediated Ferroptosis Regulation in Kidney Disease

International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 1637 - 1659

Опубликована: Фев. 1, 2025

Abstract: Kidney diseases are a significant global cause of death and disability, resulting from the destruction kidney structure function due to an imbalance between renal parenchymal cells proliferation or recruitment maladaptive cells, caused by various pathogenic factors. Currently, therapies their efficacy for limited. Ferroptosis is newly discovered iron-dependent regulated cell death. The iron homeostasis lipid metabolism affects occurrence progression triggering ferroptosis, which considered important target development disease drugs. However, in clinical practice, targeted ferroptosis therapy faces obstacles such as poor drug solubility, low resistance, imprecise targeting. With rapid nanomaterials medical field, new opportunities have emerged precise regulation treatment diseases. This article provides detailed introduction regulatory mechanisms properties nanomaterials, application diseases, with focus on discussing action therapeutic potential based aim this provide ideas directions future treatments. Keywords: nanomaterial, nanomedicine,

Язык: Английский

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Idebenone improves mitochondrial respiratory activity and attenuates oxidative damage via the SIRT3-SOD2 pathway in a prion disease cell model

Life Sciences, Год журнала: 2025, Номер 366-367, С. 123481 - 123481

Опубликована: Фев. 19, 2025

Язык: Английский

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Mitochondria-associated non-coding RNAs and their impact on drug resistance

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 26, 2025

Drug resistance is a prevalent challenge in clinical disease treatment, often leading to relapse and poor prognosis. Therefore, it crucial gain deeper understanding of the molecular mechanisms underlying drug develop targeted strategies for its effective prevention management. Mitochondria, as vital energy-producing organelles within cells, have been recognized key regulators sensitivity. Processes such mitochondrial fission, fusion, mitophagy, changes membrane potential, reactive oxygen species (ROS) accumulation, oxidative phosphorylation (OXPHOS) are all linked Non-coding RNAs (ncRNAs) enriched mitochondria (mtncRNA), whether transcribed from DNA (mtDNA) or nucleus transported mitochondria, can regulate transcription translation mtDNA, thus influencing function, including substance exchange energy metabolism. This, turn, directly indirectly affects cellular sensitivity drugs. This review summarizes types mtncRNAs associated with regulating resistance. Our aim provide insights overcoming by modulating mtncRNAs.

Язык: Английский

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Herbacetin as a Novel Ferroptosis Inhibitor for Mitigating Myocardial Damage Induced by Doxorubicin

Опубликована: Янв. 1, 2025

Язык: Английский

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USP20 mitigates doxorubicin-induced cardiotoxicity by deubiquitinating and stabilizing HuR

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Background The severe cardiotoxicity of doxorubicin (Dox) significantly restricts its clinical application. Deubiquitinating enzymes (DUBs) play pivotal roles in cardiac pathophysiology because their precise regulation protein function, localization and degradation.Objectives objective this study was to investigate the role molecular mechanism ubiquitin-specific peptidase 20 (USP20), a DUB, doxorubicin-induced cardiotoxicity.Methods Cardiomyocyte-specific USP20-knockout (USP20-CKO) mice were utilized assess USP20 cardiomyopathy (DIC). Coimmunoprecipitation (co-IP) combined with liquid chromatography‒mass spectrometry/mass spectrometry (LC‒MS/MS) analysis employed screen substrate USP20. Furthermore, mutant plasmids constructed elucidate underlying human antigen R (HuR) by Finally, an AAV9 vector used overexpress hearts cardiac-specific HuR-knockout interaction between HuR.Results results revealed decrease expression Dox-stimulated mouse cardiomyocytes. knockout resulted increased cardiomyocyte ferroptosis led DIC. Mechanistically, directly interacted HuR through protease structural domain. Deubiquitination at position 154 crucial for maintaining stability cleaving K48 ubiquitin chains inhibiting proteasomal degradation. Additionally, bound GPX4 mRNA suppress degradation, thereby mitigating contributing alleviating targeted overexpression via cardiomyocytes alleviated However, cardiomyocyte-specific knockout, no longer had anti-DIC effect, indicating that HuR, as downstream target USP20, plays irreplaceable DIC.Conclusions Our findings indicate enhances deubiquitination,

Язык: Английский

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