Effect and mechanism of PI3K/AKT/mTOR signaling pathway in the apoptosis of GC-1cells induced by nickel nanoparticles
Effect and mechanism of PI3K/AKT/mTOR signaling pathway in the apoptosis of GC-1cells induced by nickel nanoparticles
复制标题
PI3K/AKT/mTOR信号通路在镍纳米颗粒诱导GC-1细胞凋亡中的作用及机制
DOI：
10.1016/j.chemosphere.2020.126913
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发表时间：
2020
期刊：
影响因子：
8.8
通讯作者：
Lu Kong
中科院分区：
文献类型：
--
作者：
Yongya Wu;Jun Ma;Yufei Sun;Meng Tang;Lu Kong
纳米镍具有广泛的应用前景，但目前尚缺乏对其生殖系统的安全性评价。目前，由于男性不育症的发病率不断上升，男性生殖健康问题受到了广泛关注。研究表明，镍纳米颗粒会导致男性生殖毒性。本研究旨在研究镍纳米颗粒对小鼠精原细胞系GC-1细胞的毒性作用，并探讨其通过PI3K/AKT/mTOR信号通路诱导细胞凋亡的可能机制。首次在透射电子显微镜下观察了细胞的超微结构。CCK-8法检测细胞增殖，流式细胞仪检测细胞周期，流式细胞仪检测细胞凋亡率。用Western印迹和逆转录-聚合酶链式反应分别检测相关蛋白和基因的表达水平。结果表明，镍纳米颗粒不仅能引起细胞超微结构的改变，降低细胞存活率，使细胞周期停滞于G1期，而且通过抑制PI3K/AKT/mTOR信号通路，激活细胞凋亡途径。本研究结果为探索镍纳米颗粒的生殖毒性机制提供了新的思路，对制定镍纳米颗粒的安全性评价标准具有重要意义。
Nickel nanoparticles (Ni NPs) have a wide range of application prospects, but there is still a lack of their safety evaluation for the reproductive system. Nowadays, male reproductive health has been widely concerned because of the increasing incidence of male infertility. Studies have shown that Ni NPs can cause male reproductive toxicity. The purpose of this study was to investigate the toxicity of Ni NPs on GC-1 cells, a mouse spermatogonia cell line, and to explore the possible mechanism underlying the induction of apoptosis via PI3K/AKT/mTOR signaling pathway. The cell ultrastructure was firstly observed under a transmission electron microscope. Then, cell proliferation, cycle and apoptosis were detected by CCK-8 and flow cytometry, respectively. Furthermore, the expression levels of related proteins and genes were determined by Western blot and Reverse transcription-polymerase chain reaction, respectively. The results showed that Ni NPs could not only cause changes in cell ultrastructure, decreased survival rate and arrested G1 phase cell cycle, but also activated apoptosis pathway by inhibiting the PI3K/AKT/mTOR signaling pathway. The results of this study provide novel insights to explore the mechanisms of reproductive toxicity of Ni NPs and are of great significance to develop safety evaluation criteria for Ni NPs.