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球形二氧化硅纳米颗粒与神经元细胞的相互作用:尺寸依赖性毒性及钙稳态失调。

Interaction of spherical silica nanoparticles with neuronal cells: size-dependent toxicity and perturbation of calcium homeostasis.

机构信息

Dipartimento di Biologia Animale e dell'Uomo, University of Torino, Via A. Albertina 13, 10123 Torino, Italy.

出版信息

Small. 2011 Mar 21;7(6):766-74. doi: 10.1002/smll.201002287. Epub 2011 Feb 7.

Abstract

The effects of Stöber silica nanoparticles on neuronal survival, proliferation, and on the underlying perturbations in calcium homeostasis are investigated on the well-differentiated neuronal cell line GT1-7. The responses to nanoparticles 50 and 200 nm in diameter are compared. The 50-nm silica affects neuronal survival/proliferation in a dose-dependent way, by stimulating apoptotic processes. In contrast, the 200-nm silica does not show any toxic effect even at relatively high concentrations (292 μg mL−1). To identify the mechanisms underlying these effects, the changes in intracellular calcium concentration elicited by acute and chronic administration of the two silica nanoparticles are analyzed. The 50-nm silica at toxic concentrations generates huge and long-lasting increases in intracellular calcium, whereas the 200-nm silica only induces transient signals of much lower amplitude. These findings provide the first evidence that silica nanoparticles can induce toxic effects on neuronal cells in a size-dependent way, and that these effects are related to the degree of perturbation of calcium homeostasis.

摘要

我们研究了斯托伯二氧化硅纳米粒子对神经元存活、增殖的影响,以及对钙稳态下潜在扰动的影响,所用的细胞系是分化良好的 GT1-7 神经元细胞系。我们比较了直径为 50nm 和 200nm 的纳米粒子的反应。50nm 的二氧化硅纳米粒子以剂量依赖的方式影响神经元的存活/增殖,刺激细胞凋亡过程。相比之下,即使在相对较高的浓度(292μg mL−1)下,200nm 的二氧化硅纳米粒子也没有显示出任何毒性作用。为了确定这些影响的机制,我们分析了急性和慢性给予这两种二氧化硅纳米粒子后细胞内钙离子浓度的变化。在有毒浓度下,50nm 的二氧化硅纳米粒子会产生巨大且持久的细胞内钙离子增加,而 200nm 的二氧化硅纳米粒子仅诱导幅度低得多的瞬时信号。这些发现首次证明,二氧化硅纳米粒子可以以尺寸依赖的方式对神经元细胞产生毒性作用,并且这些作用与钙稳态的扰动程度有关。

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