Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China; Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China; Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
Food Chem Toxicol. 2024 Apr;186:114577. doi: 10.1016/j.fct.2024.114577. Epub 2024 Mar 6.
Silver nanoparticles (AgNPs) have been widely used in biomedicine and cosmetics, increasing their potential risks in neurotoxicity. But the involved molecular mechanism remains unclear. This study aims to explore molecular events related to AgNPs-induced neuronal damage by RNA-seq, and elucidate the role of Ca/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells synaptic degeneration induced by AgNPs. This study found that cell viabilities were decreased by AgNPs in a dose/time-dependent manner. AgNPs also increased protein expression of PINK1, Parkin, synaptophysin, and inhibited PGC-1α, MAP2 and APP protein expression, indicating AgNPs-induced synaptic degeneration involved in disturbance of mitophagy and mitochondrial biogenesis in HT22 cells. Moreover, inhibition of AgNPs-induced Ca/CaMKII activation and Drp1/ROS rescued mitophagy disturbance and synaptic degeneration in HT22 cells by reserving aforementioned protein express changes except for PGC-1α and APP protein. Thus, AgNPs-induced synaptic degeneration was mediated by Ca/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells, and mitophagy is the sensitive to the mechanism. Our study will provide in-depth molecular mechanism data for neurotoxic evaluation and biomedical application of AgNPs.
银纳米粒子（AgNPs）已广泛应用于生物医药和化妆品领域，增加了其神经毒性方面的潜在风险。但其涉及的分子机制尚不清楚。本研究旨在通过 RNA 测序探索与 AgNPs 诱导的神经元损伤相关的分子事件，并阐明 Ca/CaMKII 信号和 Drp1 依赖性线粒体紊乱在 AgNPs 诱导的 HT22 细胞突触退化中的作用。本研究发现，AgNPs 以剂量和时间依赖的方式降低细胞活力。AgNPs 还增加了 PINK1、Parkin、突触小体蛋白的蛋白表达，抑制了 PGC-1α、MAP2 和 APP 蛋白的表达，表明 AgNPs 诱导的突触退化涉及 HT22 细胞中线粒体自噬和线粒体生物发生的紊乱。此外，抑制 AgNPs 诱导的 Ca/CaMKII 激活和 Drp1/ROS 挽救了 HT22 细胞中的线粒体自噬紊乱和突触退化，保留了上述蛋白表达变化，除了 PGC-1α 和 APP 蛋白。因此，AgNPs 诱导的突触退化是由 HT22 细胞中 Ca/CaMKII 信号和 Drp1 依赖性线粒体紊乱介导的，而线粒体自噬对该机制较为敏感。我们的研究将为 AgNPs 的神经毒性评价和生物医学应用提供深入的分子机制数据。
