Aberrant cytokinesis and cell fusion result in multinucleation in HepG2 cells exposed to silica nanoparticles.
Aberrant cytokinesis and cell fusion result in multinucleation in HepG2 cells exposed to silica nanoparticles.
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DOI：
10.1021/tx500473h
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发表时间：
2015-01
影响因子：
4.1
通讯作者：
Yong-yang Yu;Junchao Duan;Weijia Geng;Qiuling Li;Lizhen Jiang;Yang Li;Yang Yu;Zhiwei Sun
中科院分区：
文献类型：
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作者：
Yong-yang Yu;Junchao Duan;Weijia Geng;Qiuling Li;Lizhen Jiang;Yang Li;Yang Yu;Zhiwei Sun
在我们以前的研究中已经确定了二氧化硅纳米颗粒（SiNPs）的多核效应，但多核效应的相关机制以及多核细胞的产生机制尚不清楚。进行该扩展研究以研究SiNP暴露后形成多核细胞的潜在机制。我们首先研究了细胞多核化，然后进行延时共聚焦成像，以证明多核细胞是由细胞融合还是异常细胞分裂引起的。我们的研究结果首次证实了SiNPs诱导HepG2细胞多核化的三种模式：细胞融合、无胞质分裂的有核分裂和胞质分裂后的融合。染色体过客复合物（CPC）缺陷和G1/S和G2/M期细胞周期阻滞可能是导致细胞异常胞质分裂的原因。MAPK/ERK 1/2信号通路的激活和有丝分裂相关蛋白的减少可能是细胞周期阻滞和多核化的机制。总之，我们证实了这样的假设，即在SiNP暴露后，异常的胞质分裂和细胞融合导致HepG2细胞中的多核化。由于细胞融合和多核化参与遗传不稳定性和肿瘤发展，因此本研究表明SiNP诱导细胞遗传不稳定性的潜在能力。这些发现引起了人们对SiNP暴露对人类健康危害和环境风险的担忧。
The multinucleation effect of silica nanoparticles (SiNPs) had been determined in our previous studies, but the relative mechanisms of multinucleation and how the multinucleated cells are generated were still not clear. This extensional study was conducted to investigate the mechanisms underlying the formation of multinucleated cells after SiNPs exposure. We first investigated cellular multinucleation, then performed time-lapse confocal imaging to certify whether the multinucleated cells resulted from cell fusion or abnormal cell division. Our results confirmed for the first time that there are three patterns contributing to the SiNPs-induced multinucleation in HepG2 cells: cell fusion, karyokinesis without cytokinesis, and cytokinesis followed by fusion. The chromosomal passenger complex (CPC) deficiency and cell cycle arrest in G1/S and G2/M checkpoints may be responsible for the cell aberrant cytokinesis. The activated MAPK/ERK1/2 signaling and decreased mitosis related proteins might be the underlying mechanism of cell cycle arrest and thus multinucleation. In summary, we confirmed the hypothesis that aberrant cytokinesis and cell fusion resulted in multinucleation in HepG2 cells after SiNPs exposure. Since cell fusion and multinucleation were involved in genetic instability and tumor development, this study suggests the potential ability of SiNPs to induce cellular genetic instability. These findings raise concerns with regard to human health hazards and environmental risks with SiNPs exposure.