<br>氧化应激驱动的线粒体损伤介导的铁蛋白吞噬参与聚苯乙烯纳米颗粒诱导的肺损伤铁死亡,ACS Nano

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氧化应激驱动的线粒体损伤介导的铁蛋白吞噬参与聚苯乙烯纳米颗粒诱导的肺损伤铁死亡
ACS Nano ( IF 15.8 ) Pub Date : 2023-12-12 , DOI: 10.1021/acsnano.3c07255
Sheng Yang ₁ , Tianyi Zhang ₁ , Yiling Ge ₁ , Yanping Cheng ₁ , Lihong Yin ₁ , Yuepu Pu ₁ , Zaozao Chen ₂ , Geyu Liang ₁

Affiliation

纳米塑料是空气中常见的污染物。然而，尚无研究关注纳米塑料暴露引起的肺损伤的毒性机制。在本研究中，聚苯乙烯纳米塑料（PS-NPs）引起肺上皮细胞铁死亡，而ferrostatin-1、去铁胺和N-乙酰半胱氨酸可以缓解这种情况。进一步研究发现，PS-NPs 扰乱线粒体结构和功能并引发自噬。从机制上讲，氧化应激引起的线粒体损伤导致铁死亡，而自噬依赖性铁蛋白自噬是关键的中间环节，导致铁蛋白降解和铁离子释放。此外，使用 Ferrostatin-1 抑制铁死亡可减轻肺部和全身毒性，从而逆转由 PS-NP 吸入引起的小鼠肺损伤。最重要的是，通过在器官水平上观察铁死亡、氧化应激和肺泡毛细血管屏障功能障碍，片上肺被进一步用来阐明铁死亡在 PS-NPs 诱导的肺损伤中的作用。总之，我们的研究表明，通过不同的肺细胞、小鼠吸入模型和基于三维的肺芯片，铁死亡是纳米塑料引起的肺损伤的重要机制，为纳米塑料的肺毒性评估提供了深入的参考。纳米塑料。

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Ferritinophagy Mediated by Oxidative Stress-Driven Mitochondrial Damage Is Involved in the Polystyrene Nanoparticles-Induced Ferroptosis of Lung Injury

Nanoplastics are a common type of contaminant in the air. However, no investigations have focused on the toxic mechanism of lung injury induced by nanoplastic exposure. In the present study, polystyrene nanoplastics (PS-NPs) caused ferroptosis in lung epithelial cells, which could be alleviated by ferrostatin-1, deferoxamine, and N-acetylcysteine. Further investigation found that PS-NPs disturbed mitochondrial structure and function and triggered autophagy. Mechanistically, oxidative stress-derived mitochondrial damage contributed to ferroptosis, and autophagy-dependent ferritinophagy was a pivotal intermediate link, resulting in ferritin degradation and iron ion release. Furthermore, inhibition of ferroptosis using ferrostatin-1 alleviated pulmonary and systemic toxicity to reverse the mouse lung injury induced by PS-NPs inhalation. Most importantly, the lung-on-a-chip was further used to clarify the role of ferroptosis in the PS-NPs-induced lung injury by visualizing the ferroptosis, oxidative stress, and alveolar-capillary barrier dysfunction at the organ level. In summary, our study indicated that ferroptosis was an important mechanism for nanoplastics-induced lung injury through different lung cells, mouse inhalation models, and three-dimensional-based lung-on-a-chip, providing an insightful reference for pulmonary toxicity assessment of nanoplastics.

更新日期：2023-12-12

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