Silica-coated magnetic nanoparticles impair proteasome activity and increase the formation of cytoplasmic inclusion bodies in vitro.
Silica-coated magnetic nanoparticles impair proteasome activity and increase the formation of cytoplasmic inclusion bodies in vitro.
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DOI：
10.1038/srep29095
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发表时间：
2016-07-05
影响因子：
4.6
通讯作者：
Lee G
中科院分区：
文献类型：
--
作者：
Phukan G;Shin TH;Shim JS;Paik MJ;Lee JK;Choi S;Kim YM;Kang SH;Kim HS;Kang Y;Lee SH;Mouradian MM;Lee G
纳米颗粒的潜在毒性，特别是对神经元的潜在毒性，是一个主要的担忧。在这项研究中，我们评估了含有罗丹明B异硫氰酸酯染料的二氧化硅包裹的磁性纳米颗粒(MNPs@SiO_2(RITC))在HEK293细胞、SH-SY5Y细胞以及大鼠原代皮质和多巴胺能神经元中的细胞毒性。与对照组和0.1 μg/μL锰纳米颗粒@二氧化硅(RITC)组相比，1.0 μg/μL锰纳米颗粒@二氧化硅(RITC)处理的细胞中，与蛋白酶体途径相关的几个基因的表达发生了改变，蛋白酶体活性显著降低。由于蛋白酶体活性的降低，在过度表达α-突触核蛋白相互作用蛋白SynPhilin-1的HEK293细胞以及原代皮质和多巴胺能神经元中，胞浆内包涵体的形成显著增加。原代神经元，尤其是多巴胺能神经元，比SH-SY5Y细胞更容易受到MNPs@SiO_2(RITC)的影响。与蛋白质聚集相关的细胞多胺在MNPs@SiO_2(RITC)处理的SH-SY5Y细胞中显著改变。这些发现突出了纳米颗粒引起的神经毒性的机制。
The potential toxicity of nanoparticles, particularly to neurons, is a major concern. In this study, we assessed the cytotoxicity of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye (MNPs@SiO2(RITC)) in HEK293 cells, SH-SY5Y cells, and rat primary cortical and dopaminergic neurons. In cells treated with 1.0 μg/μl MNPs@SiO2(RITC), the expression of several genes related to the proteasome pathway was altered, and proteasome activity was significantly reduced, compared with control and with 0.1 μg/μl MNPs@SiO2(RITC)-treated cells. Due to the reduction of proteasome activity, formation of cytoplasmic inclusions increased significantly in HEK293 cells over-expressing the α–synuclein interacting protein synphilin-1 as well as in primary cortical and dopaminergic neurons. Primary neurons, particularly dopaminergic neurons, were more vulnerable to MNPs@SiO2(RITC) than SH-SY5Y cells. Cellular polyamines, which are associated with protein aggregation, were significantly altered in SH-SY5Y cells treated with MNPs@SiO2(RITC). These findings highlight the mechanisms of neurotoxicity incurred by nanoparticles.