The role of HIF-1α in hypoxic metabolic reprogramming in osteoarthritis

Pharmacological Research, Год журнала: 2025, Номер unknown, С. 107649 - 107649

Опубликована: Фев. 1, 2025

The joint dysfunction caused by osteoarthritis (OA) is increasingly becoming a major challenge in global healthcare, and there currently no effective strategy to prevent the progression of OA. Therefore, better elucidating relevant mechanisms OA occurrence development will provide theoretical basis for formulating new prevention control strategies. Due long-term exposure cartilage tissue hypoxic microenvironment joints, metabolic reprogramming changes occur. Hypoxia-inducible factor-1alpha (HIF-1α), as core gene regulating hypoxia response vivo, plays an important regulatory role metabolism chondrocytes. HIF-1α adapts such glycolysis, oxidative phosphorylation (OXPHOS), amino acid metabolism, lipid In addition, also regulates macrophage polarization synovial inflammation, chondrocytes degeneration extracellular matrix (ECM) degradation, subchondral bone remodeling angiogenesis OA, affects pathophysiological Consequently, regulation has become therapeutic target this article reviews mechanism affecting chondrocyte reprogramming, focusing on summarizes potential ingredients or targets targeting order more beneficial treatment clinical drugs.

Язык: Английский

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Hypoxia induces ferroptotic cell death mediated by activation of the inner mitochondrial membrane fission protein MTP18/Drp1 in invertebrates

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108326 - 108326

Опубликована: Фев. 1, 2025

Hypoxia and ischemia damage sensitive organelles such as mitochondria, thus mitochondrial dysfunction contributes to metabolic disorders in crustaceans under hypoxia. The mechanisms associated with ferroptosis hypoxic have not been determined crustaceans. In particular, the early molecular events of dynamics require clarification. this study, two evolutionarily conserved fission proteins, Drp1 MTP18, were identified oriental river prawn (Macrobrachium nipponense). vitro, ferroptosis-mediated impairment membrane potential was induced by hypoxia hemocytes. hypoxia-induced hemocytes, activation increased phosphorylation at S616 identified. translocation also increased, fusion-related protein expression decreased vivo. Altered fission-fusion linked dysfunction, inducing a classic mechanism. Marf overexpression or knockdown protected against ferroptotic cell death vitro. Furthermore, verified be driven Drp1/MTP18 interaction. Under hypoxia, MTP18 transcription binding activated HIF-1α response elements (HREs) its promoter. Conjointly, resulted less apoptosis mortality gill tissue vitro; suggesting that adaptation involves vital function MTP18. conclusion, we uncovered role death. Therefore, suggest specific modulation MTP18/DRP1-mediated might therapeutic strategy stress-induced injury invertebrates.

Язык: Английский

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NINJ1 in Cell Death and Ferroptosis: Implications for Tumor Invasion and Metastasis

Cancers, Год журнала: 2025, Номер 17(5), С. 800 - 800

Опубликована: Фев. 26, 2025

NINJ1 was initially recognized for its role in nerve regeneration and cellular adhesion. Subsequent studies have uncovered participation cancer progression, where regulates critical steps tumor metastasis, such as cell migration invasion. More recently, has emerged a multifunctional protein mediating plasma membrane rupture (PMR) several lytic death processes, including apoptosis, necroptosis, pyroptosis. However, ferroptosis-an iron-dependent form of characterized by lipid peroxidation-remained unclear until 2024. Ferroptosis is suppression mechanism that may be particularly relevant to detached metastatic cells. This review explores the invasion focusing on regulation ferroptosis via non-canonical distinct from other deaths. We discuss process implications metastasis. Furthermore, we recent highlighting diverse roles regulation, canonical function PMR modulating intracellular levels glutathione (GSH) coenzyme A (CoA) interaction with xCT anti-porter. Given been associated suppression, elimination treatment-resistant cells, dormancy, NINJ1's modulation presents promising therapeutic target inhibiting Understanding dual promoting or restraining depending context could open avenues novel anti-cancer strategies enhance ferroptotic vulnerability tumors.

Язык: Английский

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p38γ modulates ferroptosis in brain injury caused by ethanol and cerebral ischemia/reperfusion by regulating the p53/SLC7A11 signaling pathway

Cellular Signalling, Год журнала: 2025, Номер unknown, С. 111728 - 111728

Опубликована: Март 1, 2025

Ischemic stroke, a neurological condition with complicated etiology that is accompanied by severe inflammation and oxidative stress, ethanol (EtOH) may aggravate ischemia/reperfusion (I/R)-induced brain damage. However, the effect of prolonged alcohol intake on acute injury remains ambiguous. As part mitogen-activated protein kinase (MAPK) family, p38γ involved in ferroptosis various diseases. This study explored how effects chronic EtOH consumption caused cerebral I/R. Brain damage was induced mice via administration liquid alcohol-containing diet for 8 weeks, middle artery occlusion reperfusion (MCAO/R), or combination both. We verified significantly exacerbated MCAO/R-induced damage, inflammation. Notably, levels were increased experimental mouse cell models. knockdown markedly attenuated tissue inflammatory infiltration + MCAO/R-treated mice. Mechanistic experiments revealed regulate through p53/SLC7A11 pathway. Overall, our results indicate crucial regulating EtOH- I/R-induced modulating

Язык: Английский

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Inhibition of GPR68 induces ferroptosis and radiosensitivity in diverse cancer cell types

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 3, 2025

Radioresistance is thought to be a major consequence of tumor milieu acidification resulting from the Warburg effect. Previously, using ogremorphin (OGM), small molecule inhibitor GPR68, an extracellular proton sensing receptor, we demonstrated that GPR68 key pro-survival pathway in glioblastoma cells. Here, demonstrate inhibition also induces ferroptosis lung cell carcinoma (A549) and pancreatic ductal adenocarcinoma (Panc02) Moreover, OGM synergized with ionizing radiation induce lipid peroxidation, hallmark ferroptosis, as well reduce colony size 2D 3D culture. not acutely detrimental but increases intracellular free ferrous iron, which known trigger reactive oxygen species (ROS) generation. In summary, peroxidation cancer cells sensitizes them part through mobilization iron. Our results suggest mediator radioresistance activated by acidic microenvironment.

Язык: Английский

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Comprehensive analysis of lncRNA and mRNA expression in triploid rainbow trout (Oncorhynchus mykiss) liver in response to chronic hypoxia

Comparative Biochemistry and Physiology Part D Genomics and Proteomics, Год журнала: 2025, Номер 54, С. 101442 - 101442

Опубликована: Фев. 9, 2025

Язык: Английский

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Epithelial-mesenchymal Transition Promotes Metabolic Reprogramming to Suppress Ferroptosis

Seminars in Cancer Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Advanced strategies in the design of Ir(III) biscyclometalated complexes for PDT

Coordination Chemistry Reviews, Год журнала: 2025, Номер 534, С. 216572 - 216572

Опубликована: Март 14, 2025

Язык: Английский

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The landscape of research on ferroptosis under hypoxic conditions: a bibliometric analysis

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 26, 2025

Background Ferroptosis is a newly identified type of iron-dependent cell death that characterized by an increase in intracellular iron ions, which disrupt the balance cellular lipid peroxidation system, causing and ultimately resulting death. Interestingly, ferroptosis modulated hypoxia plays role hypoxia-related diseases. Therefore, we performed bibliometric review Web Science Core Collection (WoSCC) database to investigate link between from January 2013 December 2023. Method The core collection within bibliographic index was consulted extract relevant articles reviews. Data on publications, countries, institutions, authors, journals, citations, keywords included studies were systematically analyzed using Microsoft Excel 2019 CiteSpace 6.3.R1 software. Result A comprehensive analysis visualization 472 research papers under hypoxic conditions published 2023 revealed emerging hotspots trends. Initially, scarcity existed this field. However, succeeded significant interest subsequent years, culminating peak 204 publications Research field focused primarily Asian region. Notably, include diseases related hypoxia, treatment therapy pathogenesis. Among researchers field, Supuran emerged as most prolific author. Wuhan University leading institution terms output, China country area study. top ten journals ranked number nine classified Q1, indicating high level credibility these studies. conducted Stockwell et al., featured journal “ Cell ,” currently has citations. Present scholarly pursuits are comprehending mechanisms through interventions affect pathway, well probing pinpointing prospective targets. Conclusion This study highlights key areas trends presence conditions, thus providing valuable insights for future directions exploration diagnosis

Язык: Английский

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Mechanism of Mitophagy to Protect Yak Kidney from Hypoxia-Induced Fibrosis Damage by Regulating Ferroptosis Pathway

Biomolecules, Год журнала: 2025, Номер 15(4), С. 556 - 556

Опубликована: Апрель 9, 2025

Renal fibrosis is a critical pathological feature of various chronic kidney diseases, with hypoxia being recognized as an important factor in inducing fibrosis. Yaks have long inhabited high-altitude hypoxic environments and do not exhibit fibrotic damage under hypoxia. However, the underlying protective mechanisms remain unclear. This study compared renal tissue structure collagen volume between low-altitude cattle yaks, revealing that yaks possess significantly higher number tubules than cattle, though showed no significant difference. Under treatment, we observed induced but did show effect suggesting adaptation may anti-fibrotic effect. Further investigation demonstrated upregulation P-AMPK/AMPK, Parkin, PINK1, LC3Ⅱ/Ⅰ, BECN1, alongside downregulation P-mTOR/mTOR yak kidneys. Additionally, hypoxia-induced tubular epithelial cells (RTECs) increased expression mitophagy-related proteins, mitochondrial membrane depolarization, lysosomes, indicating induces mitophagy. By regulating mitophagy pathway through drugs, found hypoxia, activation upregulated E-cadherin protein while downregulating Vimentin, α-SMA, Collagen I, Fibronectin. Simultaneously, there was increase SLC7A11, GPX4, GSH levels, decrease ROS, MDA, Fe2⁺ accumulation. Inhibition produced opposite effects on cellular markers. studies identified ferroptosis key mechanism promoting Moreover, models, reduced accumulation Fe2⁺, thereby alleviating ferroptosis-induced These findings suggest protects from by activating to inhibit pathway.

Язык: Английский

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