Activation of osteoblast ferroptosis via the METTL3/ASK1‐p38 signaling pathway in high glucose and high fat (HGHF)‐induced diabetic bone loss

The FASEB Journal, Год журнала: 2022, Номер 36(3)

Опубликована: Фев. 1, 2022

Diabetes mellitus (DM) and osteoporosis are two common diseases that may develop as a cause-and-effect relationship since the incidence of osteoporotic fractures is significantly increased in DM patients. However, pathophysiology diabetic yet to be clearly understood. Iron overload has been reported lead bone loss closely related osteoporosis. In this study, we hypothesized high glucose fat (HGHF) induce osteoblastic ferroptosis for pathogenesis explored possible molecular mechanisms behind. Using rat model established by HGHF feeding with subsequent intraperitoneal injection single low dose streptozocin, found serum ferritin level (a biomarker body iron store) was elevated HGHF-fed rats expression SLC7A11 GPX4 (inhibitory marker proteins ferroptosis) markedly attenuated tissue compared normal rats. an osteoblast cell model, treatment pre-osteoblastic MC3T3-E1 cells palmitic acid (HGPA) not only suppressed differentiation mineralization but also triggered ferroptosis-related death. m6A-seq revealed m6A methylation on ASK1 80.9-fold higher HGPA-treated cells. The p-ASK1 p-p38 Knockout METTL3 (methyltransferase-like 3), one major methyltransferases, abrogated HGPA-induced activation ASK1-p38 signaling pathway ferroptosis. Therefore, HGHF-induced osteoblasts main cause via METTL3/ASK1-p38 pathway, inhibition provide potential therapeutic strategy

Язык: Английский

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The role of ferroptosis mediated by NRF2/ERK-regulated ferritinophagy in CdTe QDs-induced inflammation in macrophage

Journal of Hazardous Materials, Год журнала: 2022, Номер 436, С. 129043 - 129043

Опубликована: Май 4, 2022

Язык: Английский

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Targeting Molecular Mediators of Ferroptosis and Oxidative Stress for Neurological Disorders

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 14

Опубликована: Июль 22, 2022

With the acceleration of population aging, nervous system diseases including Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), anxiety, depression, stroke, and traumatic brain injury (TBI) have become a huge burden on families society. The mechanism neurological disorders is complex, which also lacks effective treatment, so relevant research required to solve these problems urgently. Given that oxidative stress-induced lipid peroxidation eventually leads ferroptosis, both stress ferroptosis are important mechanisms causing disorders, targeting mediators hot direction at present. Our review provides current view underlying participate in potential application molecular disorders. target or agents associated with such as reactive oxygen species (ROS), nuclear factor erythroid 2–related factor-antioxidant response element (Nrf2-ARE), n-acetylcysteine (NAC), Fe2+, NADPH, its oxidases NOX, has been described this article. plays pivotal role further caused by will help provide new targets for treatment

Язык: Английский

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Nrf2: An all-rounder in depression

Redox Biology, Год журнала: 2022, Номер 58, С. 102522 - 102522

Опубликована: Окт. 31, 2022

The balance between oxidation and antioxidant is crucial for maintaining homeostasis. Once disrupted, it can lead to various pathological outcomes diseases, such as depression. Oxidative stress result in or aggravate a battery of processes including mitochondrial dysfunction, neuroinflammation, autophagical disorder ferroptosis, which have been found be involved the development Inhibition oxidative related help improve In this regard, nuclear factor erythroid 2-related 2 (Nrf2) defense system may play pivotal role. Nrf2 activation not only regulate expression series genes that reduce its damages, but also directly above combat corresponding alterations. Therefore, targeting has great potential treatment Activation antidepressant effect, specific mechanism remains elucidated. This article reviews key role depression, focusing on possible mechanisms regulating depression treatment. Meanwhile, we summarize some natural synthetic compounds therapy. All provide new insights into broad basis clinical transformation.

Язык: Английский

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Ferroptosis as a mechanism of non-ferrous metal toxicity

Archives of Toxicology, Год журнала: 2022, Номер 96(9), С. 2391 - 2417

Опубликована: Июнь 21, 2022

Язык: Английский

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Polystyrene nanoplastics-induced lung apoptosis and ferroptosis via ROS-dependent endoplasmic reticulum stress

The Science of The Total Environment, Год журнала: 2023, Номер 912, С. 169260 - 169260

Опубликована: Дек. 10, 2023

Язык: Английский

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Interferon-γ induces salivary gland epithelial cell ferroptosis in Sjogren's syndrome via JAK/STAT1-mediated inhibition of system Xc-

Free Radical Biology and Medicine, Год журнала: 2023, Номер 205, С. 116 - 128

Опубликована: Июнь 5, 2023

Язык: Английский

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Involvement of the JNK/HO‑1/FTH1 signaling pathway in nanoplastic‑induced inflammation and ferroptosis of BV2 microglia cells

International Journal of Molecular Medicine, Год журнала: 2023, Номер 52(1)

Опубликована: Июнь 1, 2023

Nanoplastics (NPs) are a newly discovered type of environmental pollutant. The potential for neurotoxicity caused by NPs and their mechanisms unclear. present study aimed to determine the molecular mechanism underlying induced NPs. Microglia (BV2) cells were used in vitro studies, it was found that invaded cells, activated inflammasomes, release significant quantities inflammatory factors detection response‑associated proteins through Western blot ELISA. By FITC, SOD, GSH, cellular iron level, ferroptosis‑related proteins, compromised anti‑oxidative increased intracellular lipid peroxidation Fe2+ concentration triggered reactions ferroptosis. Pretreatment with reactive oxygen species (ROS) inhibitor N‑acetylcysteine (NAC) alleviated induction ferroptosis cells. In addition, inhibiting expression c‑Jun N‑terminal kinase (JNK) heme oxygenase (HO‑1), resulting decreased ferroptosis, indicating JNK/HO‑1 signaling pathway involved NP‑induced effects on BV2 conclusion, could induce responses mediated may serve an important role toxicity microglia This provided novel evidence toxic highlighted theoretical mechanistic basis safe prevention treatment plastic pollution‑induced neurotoxicity.

Язык: Английский

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Fe₃O₄‐Incorporated Metal‐Organic Framework for Chemo/Ferroptosis Synergistic Anti‐Tumor via the Enhanced Chemodynamic Therapy

Advanced Healthcare Materials, Год журнала: 2024, Номер 13(14)

Опубликована: Фев. 9, 2024

Metal-organic framework (MOF)-based drug delivery nanomaterials for cancer therapy have attracted increasing attention in recent years. Here, an enhanced chemodynamic anti-tumor strategy by promoting the Fenton reaction using core-shell zeolitic imidazolate framework-8 (ZIF-8)@Fe

Язык: Английский

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Melatonin alleviates chronic stress-induced hippocampal microglia pyroptosis and subsequent depression-like behaviors by inhibiting Cathepsin B/NLRP3 signaling pathway in rats

Translational Psychiatry, Год журнала: 2024, Номер 14(1)

Опубликована: Март 27, 2024

Abstract Melatonin improves chronic stress-induced hippocampal damage and depression-like behaviors, but the mechanism needs further study. This study was to explore of melatonin inhibiting microglia pyroptosis. In virtro experiments, improved corticosterone-induced ultrastructure microstructure HAPI cells by pyroptosis, thereby increasing cell survival rate. Protein-protein interaction network molecular autodocking predicted that Cathespin B might be target inhibition NLRP3-mediated inhibited expression. Both Cathepsin inhibitor CA-074Me NLRP3 knockout Similarly, agonist Pazopanib-induced activation B/NLRP3 signaling pathway vivo studies, restraint stress (CRS)-induced alleviated pyroptosis in rats. Inhibition CRS-induced behaviors addition, These results demonstrated could alleviate pathway, improving reveals prevention treatment stress-related encephalopathy.

Язык: Английский

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