期刊
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
卷 63, 期 -, 页码 6-15出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.etap.2018.08.003
关键词
TiO2-NPs; HT22; Cells; Neurotoxicity; Endoplasmic reticulum stress; Oxidative stress; Apoptosis
资金
- Natural Science Foundation of Liaoning Province of China [201602704]
- National Natural Science Foundation of China [81403023]
- Program for Liaoning Excellent Talents in University [LJQ2015111]
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-1 alpha, 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 proapoptotic 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-i-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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