Silica nanoparticles induce multinucleation through activation of PI3K/Akt/GSK-3β pathway and downregulation of chromosomal passenger proteins in L-02 cells

  • Weijia Geng
  • Yang Li
  • Yongbo Yu
  • Yang Yu
  • Junchao Duan
  • Lizhen Jiang
  • Qiuling Li
  • Zhiwei Sun
Research Paper
First Online:
Received:
Accepted:

Abstract

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.

Keywords

Silica nanoparticles Multinucleation Reactive oxygen species Chromosomal passenger proteins PI3K/Akt/GSK-3β pathway Toxicology Health effects 
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Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81172704, No. 81230065), Special Project of Beijing Municipal Science&Technology Commission (Z131102002813060), and Project of Key Laboratory of Beijing for Toxicology.

Compliance with ethical standards

Conflict of interest

The authors declare they have no actual or potential competing financial interests.

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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Weijia Geng
    • 1
    • 2
  • Yang Li
    • 1
    • 2
  • Yongbo Yu
    • 1
    • 2
  • Yang Yu
    • 1
    • 2
  • Junchao Duan
    • 1
    • 2
  • Lizhen Jiang
    • 1
    • 2
  • Qiuling Li
    • 1
    • 2
  • Zhiwei Sun
    • 1
    • 2
  1. 1.School of Public HealthCapital Medical UniversityBeijingPeople’s Republic of China
  2. 2.Beijing Key Laboratory of Environmental ToxicologyCapital Medical UniversityBeijingPeople’s Republic of China

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