Silica nanoparticles induce multinucleation through activation of PI3K/Akt/GSK-3β pathway and downregulation of chromosomal passenger proteins in L-02 cells
Silica nanoparticles induce multinucleation through activation of PI3K/Akt/GSK-3β pathway and downregulation of chromosomal passenger proteins in L-02 cells
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DOI：
10.1007/s11051-015-3305-x
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发表时间：
2016-04
影响因子：
2.5
通讯作者：
Weijia Geng;Yang Li;Yong-yang Yu;Yang Yu;Junchao Duan;Lizhen Jiang;Qiuling Li;Zhiwei Sun
中科院分区：
文献类型：
--
作者：
Weijia Geng;Yang Li;Yong-yang Yu;Yang Yu;Junchao Duan;Lizhen Jiang;Qiuling Li;Zhiwei Sun
二氧化硅纳米颗粒（SNPs）由于其独特的物理化学特性而应用于各个领域。然而，人们对其潜在的不利影响表示关切。在我们以前的研究中，我们报道了SNPs可以诱导异常高的多核化发生率。本研究的目的是进一步探讨SNPs（68 nm）诱导人正常肝L-02细胞（L-02细胞）多核化的机制。为了确定SNPs的细胞毒性，进行MTT测定，并且细胞活力以剂量依赖性方式降低。流式细胞仪检测细胞内活性氧（ROS），Giemsa染色观察细胞多核化，结果表明，SNP暴露后细胞内ROS产生增加，多核化细胞比例增加，利用谷胱甘肽前体N-乙酰半胱氨酸（NAC）抑制ROS，探讨ROS与细胞多核化的关系。NAC的存在导致ROS的产生和多核化速率的抑制。Western blot分析显示，SNP可下调Cdc 20、Aurora B和Survivin蛋白表达，激活PI 3 K/Akt/GSK-3β信号通路。总之，SNPs诱导的多核化与PI 3 K/Akt/GSK-3β信号通路的激活以及G2/M期相关蛋白和染色体过客蛋白的下调有关。
Silica nanoparticles (SNPs) are applicable in various fields due to their unique physicochemical characteristics. However, concerns over their potential adverse effects have been raised. In our previous studies, we reported that SNPs could induce abnormal high incidence of multinucleation. The aim of this study is to further investigate the mechanisms of multinucleation induced by SNPs (68 nm) in human normal liver L-02 cells (L-02 cells). In order to determine the cytotoxicity of SNPs, MTT assay was performed, and the cell viability was decreased in a dose-dependent manner. The intracellular reactive oxygen species (ROS) detected by flow cytometry and multinucleation observed by Giemsa stain showed that ROS generation and rate of multinucleated cells increased after SNPs exposure.N-acetyl-cysteine (NAC), a glutathione precursor against SNP-induced toxicity, was used as a ROS inhibitor to elucidate the relationship between ROS and multinucleation. The presence of NAC resulted in inhibition of both ROS generation and rate of multinucleation. Moreover, Western blot analysis showed that the protein levels of Cdc20, Aurora B, and Survivin were down-regulated, and the PI3K/Akt/GSK-3β pathway was activated by SNPs. In conclusion, our findings strongly suggested that multinucleation induced by SNPs was related to PI3K/Akt/GSK-3β signal pathway activation and downregulation of G2/M phase-related protein and chromosomal passenger proteins.