Impairment of mitochondrial dynamics involved in iron oxide nanoparticle‐induced dysfunction of dendritic cells was alleviated by autophagy inhibitor 3‐methyladenine

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: mitochon...

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Veröffentlicht in:Journal of applied toxicology 2020-05, Vol.40 (5), p.631-642
Hauptverfasser: Zhang, Tian‐guang, Zhang, Yu‐long, Zhou, Qian‐qian, Wang, Xiao‐hui, Zhan, Lin‐sheng
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Sprache:eng
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Zusammenfassung: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 Fe3O4 (PEG‐Fe3O4) 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‐Fe3O4 nanoparticles impaired the functionally immature state of DCs. Autophagy inhibitor 3‐methyladenine (3‐MA) alleviated PEG‐Fe3O4 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. Iron oxide nanoparticles are adversely associated with mitochondrial toxicity. The present study showed that PEG‐COOH‐coated Fe3O4 (PEG‐Fe3O4) nanoparticles induced mitochondrial instability in dendritic cells (DCs) by promoting mitochondrial biogenesis, inhibiting mitochondrial degradation and facilitating mitochondrial fragmentation. The resulting reduced levels of dextran uptake, costimulatory molecules and chemokine receptor 7 suggested that PEG‐Fe3O4 nanoparticles impaired DC function. 3‐methyladenine alleviated PEG‐Fe3O4 nanoparticle‐induced mitochondrial instability and impairment of DC function due to enhancing the coordination of mitochondrial biogenesis and fusion.
ISSN:0260-437X
1099-1263
DOI:10.1002/jat.3933