Key Laboratory of Environmental Medicine & Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, PR China.
Key Laboratory of Environmental Medicine & Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, PR China; Testing Center for Medical Device, Yancheng Institute of Measurement and Testing, Yancheng 224007, PR China.
J Hazard Mater. 2022 Aug 15;436:129043. doi: 10.1016/j.jhazmat.2022.129043. Epub 2022 May 4.
Cadmium telluride quantum dots (CdTe QDs) exist in the environment due to the abandonment of products. There is a potential risk to organisms and toxic mechanism is worth exploring. In this study, 12.5 μmol/Kg body weight CdTe QDs triggered systemic and local inflammatory response in mice and activated macrophages, then the mechanism of activating macrophages to overexpress IL-1β and IL-6 was explored. RAW264.7 macrophages were used, and after macrophages exposing to 1 μM CdTe QDs for 24 h, oxidative stress occurred. Further investigation found that CdTe QDs triggered ferroptosis in RAW264.7 cells. And deferoxamine mesylate alleviated the excessive lipid hydroperoxide caused by QDs. Mechanistically, CdTe QDs-provoked decrease of nuclear factor erythroid 2-related factor 2 (NRF2) elicited phosphorylation of extracellular regulated protein kinases1/2 (ERK1/2) and then activated ferritinophagy, which made ferritin heavy chain 1 (FTH1) degraded in lysosome and proteasome to release free iron ions to initiate ferroptosis in macrophages. This paper updates the mechanism of macrophage activation by CdTe QDs with regard to ferritinophagy, and more importantly, identifies the key role of NRF2 and ERK1/2. Our research extends the role of ferroptosis in inflammatory responses triggered by nanoparticles (NPs) in macrophages and provides insightful reference for toxicity assessment of NPs.
碲化镉量子点（CdTe QDs）由于产品废弃而存在于环境中。它们对生物体存在潜在风险，其毒性机制值得探索。在本研究中，12.5 μmol/Kg 体重的 CdTe QDs 引发了小鼠的全身和局部炎症反应，并激活了巨噬细胞，随后探讨了激活巨噬细胞过度表达 IL-1β和 IL-6 的机制。使用 RAW264.7 巨噬细胞，在巨噬细胞暴露于 1 μM CdTe QDs 24 h 后，发生氧化应激。进一步的研究发现，CdTe QDs 诱导 RAW264.7 细胞发生铁死亡。甲磺酸去铁胺缓解了 QDs 引起的过多脂质过氧化物。在机制上，CdTe QDs 引起核因子红细胞 2 相关因子 2（NRF2）的减少，引发细胞外调节蛋白激酶 1/2（ERK1/2）的磷酸化，进而激活铁蛋白自噬，使铁蛋白重链 1（FTH1）在溶酶体和蛋白酶体中降解，释放游离铁离子，从而在巨噬细胞中引发铁死亡。本文更新了 CdTe QDs 通过铁蛋白自噬激活巨噬细胞的机制，更重要的是，确定了 NRF2 和 ERK1/2 的关键作用。我们的研究扩展了铁死亡在纳米颗粒（NPs）引发的巨噬细胞炎症反应中的作用，并为 NPs 的毒性评估提供了有价值的参考。
