Protosappanin A Protects DOX‐Induced Myocardial Injury and Cardiac Dysfunction by Targeting ACSL4/FTH1 Axis‐Dependent Ferroptosis

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 10, 2024

Abstract Doxorubicin (DOX) is an effective anticancer agent, but its clinical utility constrained by dose‐dependent cardiotoxicity, partly due to cardiomyocyte ferroptosis. However, the progress of developing cardioprotective medications counteract ferroptosis has encountered obstacles. Protosappanin A (PrA), anti‐inflammatory compound derived from hematoxylin, shows potential against DOX‐induced cardiomyopathy (DIC). Here, it reported that PrA alleviates myocardial damage and dysfunction reducing maintaining mitochondrial homeostasis. Subsequently, molecular target through proteome microarray, docking, dynamics simulation identified. Mechanistically, physically binds with ferroptosis‐related proteins acyl‐CoA synthetase long‐chain family member 4 (ACSL4) ferritin heavy chain 1 (FTH1), ultimately inhibiting ACSL4 phosphorylation subsequent phospholipid peroxidation, while also preventing FTH1 autophagic degradation release ferrous ions (Fe 2+ ) release. Given critical role in pathogenesis ischemia‐reperfusion (IR) injury, this further investigation posits can confer a protective effect IR‐induced cardiac Overall, novel pharmacological inhibitor unveiled targets uncover dual‐regulated mechanism for DIC, highlighting additional therapeutic options chemodrug‐induced cardiotoxicity ferroptosis‐triggered disorders.

Language: Английский

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Tailoring traditional Chinese medicine in cancer therapy

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 21, 2025

Language: 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, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 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

Language: Английский

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SMURF1-Induced Ubiquitination of FTH1 Disrupts Iron Homeostasis and Suppresses Myogenesis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1390 - 1390

Published: Feb. 6, 2025

Ferritin heavy chain 1 (FTH1) is pivotal in the storage, release, and utilization of iron, plays a crucial role ferroptosis pathway, exerts significant impacts on various diseases. Iron influences skeletal muscle development health by promoting cell growth, ensuring energy metabolism ATP synthesis, maintaining oxygen supply, facilitating protein synthesis. However, precise molecular mechanisms underlying iron’s regulation growth remain elusive. In this study, we demonstrated that conditional knockout (cKO) FTH1 results atrophy impaired exercise endurance. vitro studies using cKO myoblasts revealed notable decreases GSH concentrations, elevated levels lipid peroxidation, substantial accumulation Fe2+, collectively implying induction ferroptosis. Mechanistically, E3 ubiquitin-protein ligase SMURF1 (SMURF1) acts as an ubiquitin for FTH1, thereby ubiquitination subsequent degradation FTH1. Consequently, activation pathway impedes myoblast differentiation into myotubes. This study identifies novel regulator development, implicating its potential significance through iron homeostasis.

Language: Английский

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SH3GL1‐activated FTH1 inhibits ferroptosis and confers doxorubicin resistance in diffuse large B‐cell lymphoma

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: March 1, 2025

Language: Английский

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High taurocholic acid concentration induces ferroptosis by downregulating FTH1 expression in intrahepatic cholestasis of pregnancy

BMC Pregnancy and Childbirth, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 9, 2025

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder associated with and usually diagnosed based on high serum bile acid. However, pathogenesis ICP unclear. Ferroptosis has been reported as an iron-dependent mechanism cell death. Although role Ferritin Heavy Chain 1 (FTH1) in ferroptosis extensively studied various diseases, its through yet to be analyzed. Placental tissues from patients healthy controls were employed verify expression FTH1. Taurocholic acid (TCA)-induced HTR-8/SVneo cells established vitro model for ICP, ferroptosis-related experiments performed. In particular, or without overexpressing FTH1 TCA induction investigated explore relationship between during vitro, respectively. was significantly downregulated group compared control group. Furthermore, protein levels downregulated, while intracellular iron, reactive oxygen species, lipid peroxidation upregulated TCA-induced cells. contrast, inhibited by overexpression A concentration decreased Overexpression could prevent death induced TCA. Thus, inhibiting downregulation a potential therapeutic target treatment.

Language: Английский

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Punicalagin inhibits neuron ferroptosis and secondary neuroinflammation to promote spinal cord injury recovery

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114048 - 114048

Published: Jan. 18, 2025

Language: Английский

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Integrating Bulk and Single-Cell Transcriptomic Data to Identify Ferroptosis-Associated Inflammatory Gene in Alzheimer’s Disease

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 2105 - 2122

Published: Feb. 1, 2025

Background: Ferroptosis is a form of programmed cell death triggered by iron-dependent lipid peroxidation, characterized iron accumulation and elevated reactive oxygen species (ROS), leading to membrane damage. It associated with variety diseases. However, the cellular molecular links between ferroptosis, immune inflammation, brain-peripheral blood axis in Alzheimer's disease (AD) remain unclear. Methods: We integrated bulk RNA-seq data from AD brain tissue peripheral refined screening candidate genes through differential gene expression analysis, weighted co-expression network analysis (WGCNA), other approaches. Additionally, we analyzed single-cell (scRNA-seq) patients' blood, combined scRNA-seq experimental autoimmune encephalomyelitis (EAE) mouse tissue. This enabled us explore AD-related mechanisms cell-type-specific perspective. Finally, were validated ferroptosis models using reverse transcription quantitative PCR (RT-qPCR) immunofluorescence methods. Results: Bulk identified SLC11A1, an inflammatory AD. Single-cell further revealed that SLC11A1 was significantly pro-inflammatory (M1-type) microglia monocytes Moreover, microglial subpopulation M1-type highly ferroptosis. simultaneously expressed characteristic markers monocytes, suggesting these cells may originate thereby triggering neuroinflammation pathway. Cell experiments confirmed upregulated induced Conclusion: study reveals key role AD, particularly context inflammation. provides novel mechanistic perspective offers potential targets for future therapeutic strategies. Keywords: disease, RNA sequencing, microglia,

Language: Английский

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Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects

Bone Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 25, 2025

Abstract The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and activities of digestive organs. Additionally, muscle tissues serve an endocrine function secreting myogenic cytokines, thereby regulating metabolism throughout entire body. Maintaining requires iron homeostasis. Recent studies suggest that disruptions ferroptosis, form iron-dependent cell death, are essential contributors to progression wide range diseases disorders, including sarcopenia, cardiomyopathy, amyotrophic lateral sclerosis. Thus, comprehensive overview mechanisms ferroptosis these conditions is crucial for identifying potential therapeutic targets developing new strategies disease treatment and/or prevention. This review aims summarize recent advances understanding molecular underlying context injury, as well associated disorders. Moreover, we discuss within pathway possible managing Finally, shed light on current limitations future prospects interventions targeting ferroptosis.

Language: Английский

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Transcriptome analysis of multiple tissues and identification of tissue-specific genes in Lueyang black-bone chicken

Poultry Science, Journal Year: 2025, Volume and Issue: 104(4), P. 104986 - 104986

Published: March 4, 2025

Systematically constructing a gene expression atlas of poultry tissues is critically important for advancing research and production. In this study, the profiles 9 major Lueyang black-bone chicken were successfully constructed by transcriptome sequencing technology. Through in-depth analysis data, total 10 housekeeping genes (HKGs) 87 marker (MGs) identified. Furthermore, applying weighted co-expression network (WGCNA), we delineated nine tissue-specific modules 90 hub genes, offering novel insights into regulatory networks underlying expression. Kyoto Encyclopedia Genes Genomes (KEGG) enrichment showed that HKGs predominantly involved in maintaining fundamental cellular functions, with significant pathways related to oxidative phosphorylation, cell cycle regulation, DNA replication. MGs closely associated physiological providing valuable molecular mechanisms governing tissue functionality. Notably, through multidimensional validation, EEF1A1 FTH1 confirmed exhibit cross-tissue stability, establishing them as ideal reference multi-tissue qPCR experiments chickens. Additionally, identified including TNNT2, PIT54, SFTPC, PGM1, which are specific heart, liver, lung, breast muscle, respectively. The results study have scientific value expanding selection elucidating mechanisms, provide solid theoretical support technical guidance breeding improvement production practice optimization.

Language: Английский

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