Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food & Drug Administration, 3900 NCTR Rd., Jefferson, AR 72079-9502, USA.
Neurotoxicology. 2009 Nov;30(6):926-33. doi: 10.1016/j.neuro.2009.09.005. Epub 2009 Sep 23.
Nanoparticles have received a great deal of attention for producing new engineering applications due to their novel physicochemical characteristics. However, the broad application of nanomaterials has also produced concern for nanoparticle toxicity due to increased exposure from large-scale industry production. This study was conducted to investigate the potential neurotoxicity of manganese (Mn), silver (Ag), and copper (Cu) nanoparticles using the dopaminergic neuronal cell line, PC12. Selective genes associated with the dopaminergic system were investigated for expression changes and their correlation with dopamine depletion. PC12 cells were treated with 10 microg/ml Mn-40 nm, Ag-15 nm, or Cu-90 nm nanoparticles for 24 h. Cu-90 nanoparticles induced dopamine depletion in PC12 cells, which is similar to the effect induced by Mn-40 shown in a previous study. The expression of 11 genes associated with the dopaminergic system was examined using real-time RT-PCR. The expression of Txnrd1 was up-regulated after the Cu-90 treatment and the expression of Gpx1 was down-regulated after Ag-15 or Cu-90 treatment. These alterations are consistent with the oxidative stress induced by metal nanoparticles. Mn-40 induced a down-regulation of the expression of Th; Cu-90 induced an up-regulation of the expression of Maoa. This indicates that besides the oxidation mechanism, enzymatic alterations may also play important roles in the induced dopamine depletion. Mn-40 also induced a down-regulation of the expression of Park2; while the expression of Snca was up-regulated after Mn-40 or Cu-90 treatment. These data suggest that Mn and Cu nanoparticles-induced dopaminergic neurotoxicity may share some common mechanisms associated with neurodegeneration.
纳米颗粒由于其新颖的物理化学特性而备受关注，为产生新的工程应用提供了可能。然而，由于大规模工业生产导致的暴露增加，纳米材料的广泛应用也引起了人们对纳米颗粒毒性的关注。本研究旨在使用多巴胺能神经元细胞系 PC12 来研究锰（Mn）、银（Ag）和铜（Cu）纳米颗粒的潜在神经毒性。研究了与多巴胺能系统相关的选择性基因的表达变化及其与多巴胺耗竭的相关性。将 PC12 细胞用 10 μg/ml 的 Mn-40nm、Ag-15nm 或 Cu-90nm 纳米颗粒处理 24 小时。Cu-90 纳米颗粒诱导 PC12 细胞中的多巴胺耗竭，这与先前研究中 Mn-40 诱导的作用相似。使用实时 RT-PCR 检查与多巴胺能系统相关的 11 个基因的表达。Cu-90 处理后 Txnrd1 的表达上调，Ag-15 或 Cu-90 处理后 Gpx1 的表达下调。这些改变与金属纳米颗粒诱导的氧化应激一致。Mn-40 诱导 Th 的表达下调；Cu-90 诱导 Maoa 的表达上调。这表明，除了氧化机制外，酶的改变也可能在诱导的多巴胺耗竭中发挥重要作用。Mn-40 还诱导 Park2 的表达下调；而 Mn-40 或 Cu-90 处理后 Snca 的表达上调。这些数据表明，Mn 和 Cu 纳米颗粒诱导的多巴胺能神经毒性可能与神经退行性变有关的一些共同机制有关。
