氧化应激
细胞凋亡
化学
内质网
碘化丙啶
未折叠蛋白反应
免疫印迹
神经毒性
细胞生物学
活性氧
分子生物学
膜联蛋白
MTT法
生物化学
程序性细胞死亡
生物
毒性
有机化学
基因
作者
Qiong He,Xuejiao Zhou,Yang Liu,Wenfeng Gou,Junfeng Cui,Zengqiang Li,Yingliang Wu,Daiying Zuo
标识
DOI:10.1016/j.etap.2018.08.003
摘要
The purpose of this study was to explore the potential neurotoxicity and the underlying mechanism of titanium dioxide nanoparticles (TiO2-NPs) to mouse hippocampal neuron HT22 cells. We found that TiO2-NPs had concentration-dependent and time-dependent cytotoxicities to HT22 cells by the MTT assay. Propidium iodide (PI) staining with FACScan flow cytometry proved that TiO2-NPs dose-dependently increased the apoptosis rate in HT22 cells, and the apoptotic features were observed by Hochest 33258 and AO/EB staining. The levels of calcium (Ca2+) and reactive oxygen species (ROS) were significantly increased in TiO2-NPs-treated cells. Further studies by western blot and real-time QPCR proved that the protein and mRNA levels of GRP78, IRE-1α, ATF6, CHOP and caspase-12 were up-regulated after TiO2-NPs treatment, which indicates that TiO2-NPs-induced cytotoxicity is related to endoplasmic reticulum stress (ERS). Apoptosis-related protein cleaved caspase-3 and pro-apoptotic protein Bax expression levels were up-regulated, and the anti-apoptotic protein Bcl-2 expression level was down-regulated in TiO2-NPs-treated cells. The antioxidant N-acetyl-L-cysteine (NAC) can significantly reduce TiO2-NPs-induced ERS characterized by the down-regulation of GRP78 and cleaved caspase-12 levels, which indicates that oxidative stress is participated in TiO2-NPs-induced ERS. Our study suggests that TiO2-NPs-induced apoptosis in HT22 cells is through oxidative stress- and calcium imbalance-mediated ERS.
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