Laboratorio de Neurotoxicología, Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional No. 2508, Col. San Pedro Zacatenco, Apartado Postal 14-740, 07000, Mexico City, Mexico.
Neurotox Res. 2020 Feb;37(2):366-379. doi: 10.1007/s12640-019-00084-0. Epub 2019 Jul 10.
Attractive due to an alleged high biocompatibility, silica nanoparticles have been widely used in the field of nanomedicine; however, their proven capacity to induce the synthesis and release of pro-inflammatory cytokines in several cellular models has raised concern about their safety. Glutamate, the main excitatory amino acid transmitter triggers a wide variety of signal transduction cascades that regulate protein synthesis at transcriptional and translational levels. A stimulus-dependent dynamic change in the protein repertoire in neurons and glia cells is the molecular framework of higher brain functions. Within the cerebellum, Bergmann glia cells are the most abundant non-neuronal cells and span the entire molecular layer of the cerebellar cortex, wrapping the synapses in this structure. Taking into consideration the functional role of Bergmann glia in terms of the recycling of glutamate, lactate supply to neurons, and prevention of neurotoxic insults, we decided to investigate the possibility that silica nanoparticles affect Bergmann glia and by these means alter the major excitatory neurotransmitter system in the brain. To this end, we exposed cultured chick cerebellar Bergmann glia cells to silica nanoparticles and measured [S]-methionine incorporation into newly synthesized polypeptides. Our results demonstrate that exposure of the cultured cells to silica nanoparticles exerts a time- and dose-dependent modulation of protein synthesis. Furthermore, altered patterns of eukaryotic initiation factor 2 alpha and eukaryotic elongation factor 2 phosphorylation were present upon nanoparticle exposure. These results demonstrate that glia cells respond to the presence of this nanomaterial modifying their proteome, presumably in an effort to overcome any plausible neurotoxic effect.
由于据称具有较高的生物相容性,硅纳米粒子已被广泛应用于纳米医学领域;然而,它们在多种细胞模型中被证实能够诱导促炎细胞因子的合成和释放,这引起了人们对其安全性的关注。谷氨酸是主要的兴奋性氨基酸递质,它触发了广泛的信号转导级联反应,调节转录和翻译水平的蛋白质合成。神经元和神经胶质细胞中蛋白质谱的刺激依赖性动态变化是大脑高级功能的分子框架。在小脑内,Bergmann 胶质细胞是最丰富的非神经元细胞,它们跨越小脑皮层的整个分子层,将突触包裹在这个结构中。考虑到 Bergmann 胶质细胞在谷氨酸的再循环、向神经元供应乳酸盐以及防止神经毒性损伤方面的功能作用,我们决定研究硅纳米粒子是否会影响 Bergmann 胶质细胞,并通过这种方式改变大脑中的主要兴奋性神经递质系统。为此,我们将培养的鸡小脑 Bergmann 胶质细胞暴露于硅纳米粒子中,并测量[S]-甲硫氨酸掺入新合成的多肽中。我们的结果表明,培养细胞暴露于硅纳米粒子会对蛋白质合成产生时间和剂量依赖的调节。此外,纳米颗粒暴露后还存在真核起始因子 2α和真核延伸因子 2 磷酸化模式的改变。这些结果表明,胶质细胞对这种纳米材料的存在作出反应,改变其蛋白质组,可能是为了克服任何可能的神经毒性作用。