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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Eleutheroside B ameliorated high altitude pulmonary edema by attenuating ferroptosis and necroptosis through Nrf2-antioxidant response signaling

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 156, P. 113982 - 113982

Published: Nov. 7, 2022

High altitude pulmonary edema (HAPE) is a potentially fatal condition induced by exposure to high-altitude environment. Eleutheroside B naturally active polyphenolic substance that has previously demonstrated anti-inflammatory, antioxidant and antidepressant properties. However, the effects of eleutheroside on HPAE are unknown. Here, (50 mg/kg 100 mg/kg) was applied HAPE rats. alleviated lung decreased levels tumor necrosis factor-α, interleukin-1β, vascular endothelial growth factor, total proteins in bronchoalveolar lavage fluid. reversed acid-base disturbances HAPE. In addition, oxidative stress. pretreatment facilitated translocation nuclear factor E2-related 2 (Nrf2) into nucleus, contributing inhibition ferroptosis necroptosis. ML385 confirmed role Nrf2 Collectively, beneficial against were associated with necroptosis through Nrf2-antioxidant response signaling.

Language: Английский

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Ferroptosis and mitochondrial dysfunction in acute central nervous system injury

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Aug. 9, 2023

Acute central nervous system injuries (ACNSI), encompassing traumatic brain injury (TBI), non-traumatic like stroke and encephalomeningitis, as well spinal cord injuries, are linked to significant rates of disability mortality globally. Nevertheless, effective feasible treatment plans still be formulated. There primary secondary occurred after ACNSI. Most ACNSIs exhibit comparable which offer numerous potential therapeutic targets for enhancing clinical outcomes. Ferroptosis, a newly discovered form cell death, is characterized lipid peroxidation process that dependent on iron oxidative conditions, also indispensable mitochondria. Ferroptosis play vital role in many neuropathological pathways, may induce mitochondrial dysfunction, thereby indicating the essentiality connection ferroptosis ACNSIs. there remains lack clarity regarding involvement mitochondria occurrence In recent studies, anti-ferroptosis agents such inhibitor Ferrostain-1 chelation therapy have shown ameliorating deleterious effects cases The importance this evidence extremely relation research control Therefore, our review aims provide researchers focusing outcomes with valuable insights by summarizing physiopathological mechanisms exploring correlation between ferroptosis,

Language: Английский

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Potential therapeutic effects of traditional Chinese medicine in acute mountain sickness: pathogenesis, mechanisms and future directions

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: June 4, 2024

Background and objectives Acute mountain sickness (AMS) is a pathology with different symptoms in which the organism not adapted to environment that occurs under special of high altitude. Its main mechanism organism’s tissue damage caused by acute hypobaric hypoxia. Traditional Chinese medicine (TCM) theory focuses on holistic concept. TCM has made remarkable achievements treatment many sicknesses. This review outlines pathogenesis AMS modern traditional medicine, progress animal models AMS, summarizes therapeutic effects AMS. Methods Using keywords “traditional medicine,” “herbal “acute sickness,” “high-altitude pulmonary edema,” cerebral hypoxia,” “high-altitude,” all relevant literature published up November 2023 were collected from Scopus, Web Science, PubMed, China National Knowledge Infrastructure databases, key information was analyzed. Results We systematically summarised hypoxia tissues organism, study methodology for establishment an model retrieved 18 proprietary medicines clinical The principle mainly invigorating qi, activating blood removing stasis. components botanical drugs include salidroside, ginsenoside Rg1, tetrahydrocurcumin. action through regulation HIF-1α/NF-κB signaling pathway, inhibition inflammatory response oxidative stress, enhancement energy metabolism. Conclusion unclear. Still, formulas have been used treat multifaceted interventions, such as compound danshen drip pills, Huangqi Baihe granules, Rg1. These generally exert anti-AMS pharmacological inhibiting expression VEGF, concentration MDA pro-inflammatory factors, down-regulating NF-κB/NLRP3 promoting SOD Na + -K -ATPase activities, attenuates hypoxia-induced injury. comprehensively analyses application makes suggestions more in-depth studies future, aiming provide some ideas insights subsequent studies.

Language: Английский

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Acute high‐altitude hypoxia exposure causes neurological deficits via formaldehyde accumulation

CNS Neuroscience & Therapeutics, Journal Year: 2022, Volume and Issue: 28(8), P. 1183 - 1194

Published: May 18, 2022

Abstract Introduction Acute high‐altitude hypoxia exposure causes multiple adverse neurological consequences. However, the exact mechanisms are still unclear, and there is no targeted treatment with few side effects. Excessive cerebral formaldehyde (FA) impairs numerous functions, can be eliminated by nano‐packed coenzyme Q10 (CoQ10). Aims In this study, we aimed to investigate whether FA was accumulated after hypobaric exposure, further explored preventative effect of CoQ10 through elimination. Results Accumulated found in C57BL/6 mice acute which resulted metabolic disturbance elevation semicarbazide‐sensitive amine oxidase, declination aldehyde dehydrogenase‐2. also induce neuronal ferroptosis vivo. Excitingly, administration for 3 days before reduced accumulation, alleviated subsequent ferroptosis, preserved functions. Conclusion Cerebral accumulation mediates deficits under hypoxia, supplementation may a promising strategy visitors sojourners at plateau.

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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Dynamic proteomic and phosphoproteomic analysis reveals key pathways and targets in the early stages of high-altitude traumatic brain injury

Experimental Neurology, Journal Year: 2025, Volume and Issue: 386, P. 115147 - 115147

Published: Jan. 16, 2025

Language: Английский

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Bee Pollen Potential to Modulate Ferroptosis: Phytochemical Insights for Age-Related Diseases

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 265 - 265

Published: Feb. 25, 2025

Bee pollen (BP) is one of the richest known natural resources micronutrients and bioactive phytochemicals. Some captivating bioactivities BP compounds, although being largely investigated for latter as individual molecules, remain very scarcely or completely uninvestigated in bee a whole product. Among most intriguing these bioactivities, we identified ferroptosis major one. Ferroptosis, recently discovered form cell death (connecting oxidative stress inflammation), complex pathophysiological process crucial perplexing events current challenging human diseases such cancer, neurodegeneration, general aging diseases. Many compounds were found to intricately modulate depending on cellular context by inducing this mechanism malignant cells preventing it non-malignant cells. Since research both fields, i.e., ferroptosis, still recent, deemed necessary undertake review figure out extent potential modulating mechanisms. Our proved that wide range (polyphenols, phenolamides, carotenoids, vitamins, minerals, others) substantially diverse Accordingly, phytochemicals nutrients showed interesting preclinical studies lead ferroptosis-mediated outcomes important processes, including many aging-related disorders. One paramount challenges be resolved determine how different act biological contexts, either through synergistic antagonistic behaviors. We hope our work constitutes valuable incentive future investigations promising relevant avenue.

Language: Английский

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High-Altitude Hypoxia Exposure Induces Iron Overload and Ferroptosis in Adipose Tissue

Antioxidants, Journal Year: 2022, Volume and Issue: 11(12), P. 2367 - 2367

Published: Nov. 29, 2022

High altitude (HA) has become one of the most challenging environments featuring hypobaric hypoxia, which seriously threatens public health, hence its gradual attraction attention over past decade. The purpose this study is to investigate effect HA hypoxia on iron levels, redox state, inflammation, and ferroptosis in adipose tissue. Here, 40 mice were randomly divided into two groups: sea-level group (altitude 5000 m, treatment for 4 weeks). Total contents, ferrous ROS generation, lipid peroxidation, oxidative enzyme system, proinflammatory factor secretion, ferroptosis-related biomarkers examined, respectively. According results, exposure increases total levels both WAT BAT. Meanwhile, release, MDA, 4-HNE elevation, GSH depletion, as well decrease SOD, CAT, GSH-Px activities further evidenced a phenotype imbalance tissue during exposure. Additionally, secretion inflammatory factors was also significantly enhanced mice. Moreover, remarkably changed expression markers suggested that increased sensitivity Overall, reveals capable inducing imbalance, response, ferroptosis, driven part by changes overload, expected provide novel preventive targets HA-related illness.

Language: Английский

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Effects of Hypoxemia by Acute High-Altitude Exposure on Human Intestinal Flora and Metabolism

Microorganisms, Journal Year: 2023, Volume and Issue: 11(9), P. 2284 - 2284

Published: Sept. 11, 2023

This study examined the effects of hypoxemia caused by acute high-altitude hypoxia (AHAH) exposure on human intestinal flora and its metabolites. The changes in flora, metabolism, erythropoietin content AHAH population under altitude conditions were comprehensively analyzed using 16S rRNA sequencing, metabonomics, content. results showed that compared with those control group (C group), metabolites (D group) altered. We found alterations according to metabolic marker tyrosine through random forest ROC analyses. Fecal serum metabonomics analyses revealed microbial could be absorbed into blood participate metabolism. Finally, a significant correlation between (EPO) was found, which shows can help confront stress regulating EPO levels. Our findings provide new insights adaptive mechanism prevention AHAH.

Language: Английский

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