The apoptosis induced by silica nanoparticle through endoplasmic reticulum stress response in human pulmonary alveolar epithelial cells
The apoptosis induced by silica nanoparticle through endoplasmic reticulum stress response in human pulmonary alveolar epithelial cells
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纳米二氧化硅通过内质网应激反应诱导人肺泡上皮细胞凋亡
DOI：
10.1016/j.tiv.2019.01.009
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发表时间：
2019
影响因子：
3.2
通讯作者：
Tang Meng
中科院分区：
文献类型：
--
作者：
Wu Tianshu;Zhang Shihan;Liang Xue;He Keyu;Wei Tingting;Wang Yan;Zou Lingyue;Zhang Ting;Xue Yuying;Tang Meng
近年来，二氧化硅纳米粒子（SiO2-NPs）和介孔二氧化硅纳米粒子（mSiO 2-NPs）由于其特殊的理化性质，在生物传感器、药物输送和生物活性剂载体等生物医学领域的应用日益增多。然而，对它们的生物安全评估远远落后于它们的快速应用。在这项研究中，我们观察到SiO2-NPs和mSiO 2-NPs在一定暴露剂量下降低了人肺泡上皮细胞（HPAEpiC）的细胞活力，同时增加了细胞凋亡率。在相同的处理剂量下，mSiO 2-NPs的毒性比SiO2-NPs小，mSiO 2-NPs在生物医学领域具有良好的应用前景。由于两种SiO2-NPs均能被摄入细胞内，并在内质网（ER）中积累，导致细胞病理形态学改变和亚细胞器损伤，我们推测内质网应激反应可能参与了NPs诱导的细胞凋亡。结果表明，SiO2-NPs和mSiO 2-NPs暴露增加了两种ER应激标志物的表达水平，例如BiP和CHOP，这可以被ER应激抑制剂4-PBA抑制，随后HPAEpiC的凋亡率降低。尽管目前还不清楚纳米颗粒引起细胞凋亡后内质网应激反应的直接靶点，但我们的研究结果为研究人员探索SiO2-NPs和mSiO 2-NPs的毒性机制提供了新的见解，以减少它们的不良影响。
Recently, the use of silica nanoparticles (SiO2-NPs) and mesoporous silica nanoparticles (mSiO2-NPs) in the biomedical field, such as biosensors, drug deliveries and bioactivator carriers, is increasing due to their special physiochemical properties. However, the biosafety assessment of them is far lagging behind their rapid application. In this study, we observed that both SiO2-NPs and mSiO2-NPs with certain exposed doses decreased the cell viability while increased the apoptosis rates in the human pulmonary alveolar epithelial cells (HPAEpiC). Generally, mSiO2-NPs presented less toxic effects than SiO2-NPs with same treated dose, which assures the positive application prospect of mSiO2-NPs in the area of biomedicine. Since both SiO2-NPs could be taken into cells and accumulated in the endoplasmic reticulum (ER), which resulted in pathologically morphological changes and subcellular organelle damages, we hypothesized that the ER stress response could be involved in the NPs-induced apoptosis. The findings suggested that SiO2-NPs and mSiO2-NPs exposure increased the expression levels of two ER stress markers, e.g. BiP and CHOP, which could be inhibited by the ER stress inhibitor 4-PBA, following with decreased apoptosis rates in HPAEpiC. Even though it is still unclear of the direct target of NPs causing ER stress response following with cell apoptosis, our findings provide a novel insight for researchers to explore the toxic mechanisms of SiO2-NPs and mSiO2-NPs in order to reduce the adverse effects of them.