Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles
Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles
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DOI：
10.1016/j.yexcr.2004.12.021
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发表时间：
2005-04-15
影响因子：
3.7
通讯作者：
von Mikecz, A
中科院分区：
文献类型：
--
作者：
Chen, M;von Mikecz, A
尽管纳米粒子的使用呈指数级增长，但人们对纳米粒子的细胞生物学效应知之甚少。在这里，我们报告的二氧化硅（SiO2）纳米粒子的细胞核中，他们诱导异常簇的拓扑异构酶I（拓扑异构酶1）的核质中，另外还包含签名蛋白的核结构域，蛋白质聚集，如泛素，蛋白酶体，细胞谷氨酰胺重复（polyQ）蛋白，和亨廷顿蛋白。核内蛋白聚集体的形成（1）抑制复制、转录和细胞增殖;（2）不显著改变蛋白酶体活性或细胞活力;（3）可被刚果红和海藻糖逆转。由于SiO2纳米颗粒引发的亚核病理学类似于扩展的聚谷氨酰胺神经退行性疾病中发生的病理学，我们建议应使用细胞核功能结构的完整性作为细胞毒性的读数，并在安全纳米技术的开发中考虑。(c)2004年爱思唯尔公司All rights reserved.
Despite of their exponentially growing use, little is known about cell biological effects of nanoparticles. Here, we report uptake of silica (SiO2) nanoparticles to the cell nucleus where they induce aberrant clusters of topoisomerase I (topo 1) in the nucleoplasm that additionally contain signature proteins of nuclear domains, and protein aggregation such as ubiquitin, proteasomes, cellular glutamine repeat (polyQ) proteins, and huntingtin. Formation of intranuclear protein aggregates (1) inhibits replication, transcription, and cell proliferation; (2) does not significantly alter proteasomal activity or cell viability; and (3) is reversible by Congo red and trehalose. Since SiO2 nanoparticles trigger a subnuclear pathology resembling the one occurring in expanded polyglutamine neurodegenerative disorders, we suggest that integrity of the functional architecture of the cell nucleus should be used as a read out for cytotoxicity and considered in the development of safe nanotechnology. (c) 2004 Elsevier Inc. All rights reserved.