Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
Environ Toxicol. 2022 May;37(5):1093-1103. doi: 10.1002/tox.23467. Epub 2022 Jan 21.
Exposure to nickel oxide nanoparticles (NiONPs), which have been widely produced and applied in industry, leads to adverse pulmonary and systemic effects. The aim of this study is to investigate the involvement of apoptosis and ferroptosis in NiONPs-induced acute lung injury (ALI). Intratracheal instillation of NiONPs into mice elevated the levels of pro-inflammatory cytokines, neutrophils, and proteins in the bronchoalveolar lavage fluid, and triggered apoptosis and ferroptosis in the lung tissues. Consistently, NiONPs-induced apoptosis and ferroptosis were observed in in vitro experiments using human lung epithelial cells. Activating transcription factor 3 (ATF3), a stress-inducible transcription factor, was upregulated by NiONPs exposure in both murine lung tissues and human lung epithelial cells. Moreover, human lung epithelial cells with ATF3 deficiency exhibited a lower level of apoptosis and ferroptosis when exposed to NiONPs. Collectively, our findings demonstrated that ATF3 was responsive to NiONPs exposure, and promoted NiONPs-induced apoptosis and ferroptosis in lung epithelial cells, indicating that ATF3 is a potential biomarker and therapeutic target for NiONPs-associated ALI.
接触镍氧化物纳米颗粒（NiONPs）会导致肺部和全身的不良反应，这些纳米颗粒已经广泛应用于工业生产。本研究旨在探讨细胞凋亡和铁死亡在 NiONPs 诱导的急性肺损伤（ALI）中的作用。通过气管内滴注 NiONPs 到小鼠体内，会导致促炎细胞因子、中性粒细胞和支气管肺泡灌洗液中的蛋白质水平升高，并引发肺组织中的细胞凋亡和铁死亡。同样，在体外用人肺上皮细胞进行的实验中也观察到了 NiONPs 诱导的细胞凋亡和铁死亡。应激诱导转录因子 3（ATF3）是一种应激诱导的转录因子，NiONPs 暴露会使其在小鼠肺组织和人肺上皮细胞中上调。此外，当人肺上皮细胞 ATF3 缺失时，暴露于 NiONPs 后细胞凋亡和铁死亡水平降低。总之，我们的研究结果表明，ATF3 对 NiONPs 暴露有反应，并促进肺上皮细胞中的 NiONPs 诱导的细胞凋亡和铁死亡，提示 ATF3 是 NiONPs 相关 ALI 的潜在生物标志物和治疗靶点。
