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首页> 外文期刊>Journal of applied toxicology >Impairment of mitochondrial dynamics involved in iron oxide nanoparticle‐induced dysfunction of dendritic cells was alleviated by autophagy inhibitor 3‐methyladenine
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Impairment of mitochondrial dynamics involved in iron oxide nanoparticle‐induced dysfunction of dendritic cells was alleviated by autophagy inhibitor 3‐methyladenine

机译:通过自噬抑制剂3-甲基腺嘌呤减轻了氧化铁纳米粒子诱导的树突细胞功能障碍的线粒体动力学的损伤

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Abstract Iron oxide nanoparticles are nanomaterials that are used extensively in the biomedical field, but they are associated with adverse effects, including mitochondrial toxicity. Mitochondrial homeostasis is achieved through dynamic stability based on two sets of antagonistic balanced processes: mitochondrial biogenesis and degradation as well as mitochondrial fission and fusion. In this study, we showed that PEG‐COOH‐coated Fe 3 O 4 (PEG‐Fe 3 O 4 ) nanoparticles induced mitochondrial instability in dendritic cells (DCs) by impairing mitochondrial dynamics due to promotion of mitochondrial biogenesis through activation of the peroxisome proliferator‐activated receptor γ coactivator 1α (PGC1α) pathway, inhibiting mitochondrial degradation via decreased autophagy, and facilitating mitochondrial fragmentation involving increased levels of DRP1 and MFN2. The resulting reduced levels of dextran uptake, CD80, CD86 and chemokine receptor 7 (CCR7) suggested that PEG‐Fe 3 O 4 nanoparticles impaired the functionally immature state of DCs. Autophagy inhibitor 3‐methyladenine (3‐MA) alleviated PEG‐Fe 3 O 4 nanoparticle‐induced mitochondrial instability and impairment of the functionally immature state of DCs due to unexpected enhancement of PGC1α/MFN2‐mediated coordination of mitochondrial biogenesis and fusion.
机译:摘要氧化铁纳米粒子是纳米材料,其在生物医学领域广泛使用,但它们与不良反应有关,包括线粒体毒性。基于两组拮抗均衡过程的动态稳定性实现了线粒体稳定性:线粒体生物发生和降解以及线粒体裂变和融合。在该研究中,我们展示了通过通过活化过氧化物激素激活的激活而损害线粒体动态,PEG-CoOH涂覆的Fe 3 O 4(PEG-Fe 3 O 4)纳米颗粒在树突式细胞(DCS)中诱导线粒体不稳定性 - 活化的受体γ共粘膜1α(PGC1α)途径,抑制通过降低的自噬降低的线粒体降解,并促进涉及DRP1和MFN2水平增加的线粒体碎片。由此产生的葡聚糖摄取水平降低,CD80,CD86和趋化因子受体7(CCR7)表明PEG-FE 3 O 4纳米颗粒损害了DC的功能性未成熟状态。自噬抑制剂3-甲基腺嘌呤(3-mA)缓解PEG-Fe 3 O 4纳米颗粒诱导的线粒体不稳定性,由于PGC1α/ MFN2介导的线粒体生物发生和融合的协调意外增强,DC的功能不成熟状态的损伤。

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