通过NCOA4介导的费里替诺法基调节了肺细胞中AgNP诱导的费洛化
Rui Zhang1, Haitao Yang1, Menghao Guo1
1Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.
概括
银纳米粒子 (AgNPs) 通过触发铁亡,一种细胞死亡途径,涉及铁过载,从而导致肺损伤. 通过NCOA4介导的费里替诺法基是AgNP诱导的肺毒性的关键机制.
科学领域:
- 纳米技术 纳米技术
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
背景情况:
- 银纳米粒子 (AgNPs) 由于其抗菌性质,具有广泛的工业和医疗应用.
- 有关AgNP的健康风险存在担忧,特别是肺部毒性,因为呼吸系统易受暴露的影响.
- 铁亡与AgNP诱导的肺损伤有关,但其潜在的分子机制需要进一步阐明.
研究的目的:
- 调查铁亡的作用,特别是NCOA4调节的铁消化,在AgNP诱导的肺毒性.
- 阐明AgNP在肺细胞中触发铁亡的分子机制.
- 探索减轻AgNP引起的肺损伤的潜在治疗点.
主要方法:
- 在体外和体外模型被用于评估AgNP细胞毒性和肺损伤.
- 研究了铁的失调,NCOA4介导的费里丁,谷氨 (GSH) 水平,活性氧物种 (ROS) 和脂质过氧化.
- 使用铁灭菌抑制剂 (Fer-1,DFO),NCOA4 siRNA和自调节剂 (3-MA,Rapa) 来检查铁灭菌途径.
主要成果:
- AgNPs诱导了剂量依赖的细胞毒性和肺损伤,其特征是通过NCOA4介导的费里丁菌性铁过载.
- 暴露于AgNP导致GSH耗尽,ROS和MDA水平增加,以及脂质过氧化,激活铁亡级联.
- 铁亡抑制剂,NCOA4倒置和自抑制显著减弱了AgNP诱导的铁亡和肺损伤.
结论:
- 铁亡是AgNP诱导的肺毒性的一个关键机制.
- 通过NCOA4介导的费里替诺法基在促进AgNP诱导的铁灭菌中起着至关重要的作用.
- 这些发现提供了对AgNP肺部毒性的机制性见解,并建议NCOA4作为潜在的治疗点.
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