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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Ferroptosis Regulated by Hypoxia in Cells

Cells, Journal Year: 2023, Volume and Issue: 12(7), P. 1050 - 1050

Published: March 30, 2023

Ferroptosis is an oxidative damage-related, iron-dependent regulated cell death with intracellular lipid peroxide accumulation, which associated many physiological and pathological processes. It exhibits unique features that are morphologically, biochemically, immunologically distinct from other forms. by iron metabolism, anti-oxidant defense systems, as well various signal pathways. Hypoxia, found in a group of conditions, can affect multiple cellular functions activation the hypoxia-inducible factor (HIF) signaling mechanisms. Emerging evidence demonstrated hypoxia regulates ferroptosis certain types conditions. In this review, we summarize basic mechanisms regulations hypoxia, regulation may contribute to numerous diseases therapies.

Language: Английский

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Hypoxia and ferroptosis

Cellular Signalling, Journal Year: 2024, Volume and Issue: 122, P. 111328 - 111328

Published: Aug. 1, 2024

Ferroptosis is a novel, iron-dependent cell death characterized by the excessive accumulation of ferroptosis lipid peroxides ultimately leading to oxidative damage membrane. Iron, lipid, amino acid metabolism, and other signaling pathways all control ferroptosis. Numerous bodily tissues experience hypoxia under normal pathological circumstances. Tissue cells can adjust these changes activating hypoxia-inducible factor (HIF) pathway mechanisms in response hypoxic environment. In recent years, there has been increasing evidence that are closely linked, regulate specific conditions through different pathways. this paper, we review possible positive negative regulatory factors, as well ferroptosis-associated ischemic diseases, with intention delivering novel therapeutic avenues for defense management illnesses linked

Language: Английский

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Ligustrazine hydrochloride Prevents Ferroptosis by Activating the NRF2 Signaling Pathway in a High-Altitude Cerebral Edema Rat Model

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1110 - 1110

Published: Jan. 27, 2025

High-altitude cerebral edema (HACE) is a disorder caused by low pressure and hypoxia at high altitudes. Nevertheless, as of now, there still scarcity safe effective prevention treatment methods. The active component Ligusticum Chuanxiong, namely Ligustrazine hydrochloride (LH), has shown potential in the HACE due to its anti-inflammatory, antioxidant, neuroprotective effects nervous system disorders. Consequently, protective effect LH on mechanism need be further explored. Prior modeling, 90 male Sprague-Dawley rats were pretreated with different doses drugs, including (100 mg/kg 50 mg/kg), dexamethasone (4 ML385 (30 mg/kg). Subsequently, placed low-pressure anoxic chamber simulating plateau environment establish rat model. mechanisms elucidated through determination brain water content, HE staining, ELISA, immunofluorescence, molecular docking, dynamics simulation, western blot, other techniques. results showed, first all, that pretreatment can effectively reduce content; down-regulate expression AQP4, HIF-1α, VEGF proteins; alleviate damage tissue nerve cells. Secondly, compared group, significantly MDA levels increase GSH SOD levels. Additionally, decreased inflammatory factors IL-1β, IL-6, TNF-α; reduced total iron content tissue; increased ferroptosis-related proteins such SLC7A11, GPX4, FTH1; alleviated ferroptosis occurrence. Molecular docking simulations show strong binding affinity for NRF2 signaling. Western blot analysis confirmed promotes translocation from cytoplasm nucleus activates signaling pathway exert an antioxidant effect. inhibitor reverse anti-oxidative stress tissue. In summary, may have activating pathway, inhibiting ferroptosis, resisting oxidative stress.

Language: Английский

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Notoginsenoside R1 treatment facilitated Nrf2 nuclear translocation to suppress ferroptosis via Keap1/Nrf2 signaling pathway to alleviated high-altitude myocardial injury

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116793 - 116793

Published: May 21, 2024

High-altitude myocardial injury (HAMI) represents a critical form of altitude illness for which effective drug therapies are generally lacking. Notoginsenoside R1, prominent constituent derived from Panax notoginseng, has demonstrated various cardioprotective properties in models ischemia/reperfusion injury, sepsis-induced cardiomyopathy, cardiac fibrosis, and injury. The potential utility notoginsenoside R1 the management HAMI warrants prompt investigation. Following successful construction model, series experimental analyses were conducted to assess effects at dosages 50 mg/Kg 100 mg/Kg. results indicated that exhibited protective against hypoxic by reducing levels CK, CK-MB, LDH, BNP, leading improved function decreased incidence arrhythmias. Furthermore, was found enhance Nrf2 nuclear translocation, subsequently regulating SLC7A11/GPX4/HO-1 pathway iron metabolism mitigate ferroptosis, thereby mitigating inflammation oxidative stress induced high-altitude conditions. In addition, application ML385 confirmed involvement translocation therapeutic approach HAMI. Collectively, advantageous impacts on have been linked suppression ferroptosis via signaling.

Language: Английский

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Ferroptosis pathways: Unveiling the neuroprotective power of cistache deserticola phenylethanoid glycosides

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 333, P. 118465 - 118465

Published: June 27, 2024

Cistanche deserticola is a kind of parasitic plant living in the roots desert trees. It rare Chinese medicine, which has effect tonifying kidney Yang, benefiting essence and blood moistening intestinal tract. Cistache phenylethanoid glycoside (PGS), an active component found Ma, have potential tonifying, intellectual enhancing, neuroprotective effects. total capsule been marketed to treat vascular dementia disease. To identify renal, enhancing effects PGS explore exact targets mechanisms PGS. This study systematically investigated four types pathways leading ferroptosis through transcriptome, metabolome, ultrastructure molecular biology techniques explored mechanism by multiple synergistically exert on hypoxia. alleviated learning memory dysfunction pathological injury mice exposed hypobaric hypoxia attenuating hypoxia-induced hippocampal histopathological damage, impairing blood‒brain barrier integrity, increasing oxidative stress levels, expression cognitive proteins. reduced formation lipid peroxides improved upregulating GPX-4/SCL7A311 axis downregulating ACSL4/LPCAT3/LOX axis. also facilitating cellular Fe2+ efflux regulating mitochondrial transport effectively antagonized cell induced erastin (a inducer). demonstrated prevents hypoxic nerve pathways, achieved mice. provides theoretical basis for development application

Language: Английский

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Inhibition of NSUN6 protects against intermittent hypoxia-induced oxidative stress and inflammatory response in adipose tissue through suppressing macrophage ferroptosis and M1 polarization

Life Sciences, Journal Year: 2025, Volume and Issue: 364, P. 123433 - 123433

Published: Jan. 28, 2025

Language: Английский

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Neuroprotective effect and possible mechanism of edaravone in rat models of spinal cord injury: a systematic review and network meta-analysis

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 7, 2025

Objective The present review was developed to critically evaluate the neuroprotective effects of edaravone for experimental rat models spinal cord injury (SCI) and generalize possible mechanisms. Methods Systematic searches were carried out on databases including PubMed, Embase, Web Science, Scopus, Cochrane Library from their inception March 2024. Controlled studies that assessed neurological roles rats following SCI selected. Basso, Beattie, Bresnahan (BBB) locomotor rating scale, residual white matter area, malondialdehyde (MDA) level systematically searched by two reviewers. Results Ten eligible publications included. Meta-analyses showed increased BBB scores in edaravone-treated compared with control ones. effect size gradually day 7 (seven studies, n = 246, weighted mean difference (WMD) 1.96, 95% confidence interval (CI) 1.23 2.68, P < 0.00001) 28 222, WMD 4.41, CI 3.19 5.63, after then maintained stably time. Meanwhile, treatment associated an amendment spared area a lowering MDA expression lesion area. subgroup analyses revealed treated exhibited superior recovery compression than contusion In network analyses, surface under cumulative ranking curve up dose 5–6 mg/(kg·d) edaravone, which it plateaued. Mechanism analysis suggested can ameliorate oxidative stress, mitigate neuroinflammation, counteract neuron apoptosis ferroptosis via multiple signaling pathways exert its effects. Conclusion Collectively, protective systematic action mechanism, warrants further investigation research treatment. Nonetheless, light limitations included findings this should be interpreted caution. Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42022374914 .

Language: Английский

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Protective effects of Eleutheroside E against high-altitude pulmonary edema by inhibiting NLRP3 inflammasome-mediated pyroptosis

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115607 - 115607

Published: Sept. 28, 2023

Eleutheroside E (EE) is a primary active component of Acanthopanax senticosus, which has been reported to inhibit the expression inflammatory genes, but underlying mechanisms remain elusive. High-altitude pulmonary edema (HAPE) severe complication high-altitude exposure occurring after ascent above 2500 m. However, effective and safe preventative measures for HAPE still need be improved. This study aimed elucidate potential mechanism EE in HAPE. Rat models were established through hypobaric hypoxia. Mechanistically, hypoxia aggravates oxidative stress upregulates (pro)-inflammatory cytokines, activating NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis, eventually leading suppressed NLRP3 pyroptosis by inhibiting nuclear translocation factor kappa-Β (NF-κB), thereby protecting lung from nigericin (Nig), an activator, partially abolished protective effects EE. These findings suggest promising agent preventing induced pyroptosis.

Language: Английский

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Iron: The silent culprit in your adipose tissue

Obesity Reviews, Journal Year: 2023, Volume and Issue: 25(1)

Published: Oct. 3, 2023

Summary Iron plays a vital role in essential biological processes and requires precise regulation within the body. Dysregulation of iron homeostasis, characterized by increased serum ferritin levels excessive accumulation liver, adipose tissue, skeletal muscle, is associated with obesity insulin resistance. Notably, excess tissue promotes dysfunction. As optimal function crucial for maintaining healthy phenotype obesity, comprehensive understanding homeostasis imperative designing new therapeutic approaches to improve prevent Here, we conducted review relevant studies, focusing on providing valuable insights into intricate interplay between tissue. It sheds light impact adipogenesis physiology both white brown Furthermore, highlight critical key modulators, such as cytosolic aconitase, mitochondria, macrophages,

Language: Английский

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