Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Centre for Disease Control and Prevention, No, 21, Road 1st Tianbei, Luohu District, Shenzhen, 518020, PR China.
Part Fibre Toxicol. 2010 Jan 19;7:1. doi: 10.1186/1743-8977-7-1.
Nanometer silicon dioxide (nano-SiO2) has a wide variety of applications in material sciences, engineering and medicine; however, the potential cell biological and proteomic effects of nano-SiO2 exposure and the toxic mechanisms remain far from clear.
Here, we evaluated the effects of amorphous nano-SiO2 (15-nm, 30-nm SiO2). on cellular viability, cell cycle, apoptosis and protein expression in HaCaT cells by using biochemical and morphological analysis, two-dimensional differential gel electrophoresis (2D-DIGE) as well as mass spectrometry (MS). We found that the cellular viability of HaCaT cells was significantly decreased in a dose-dependent manner after the treatment of nano-SiO2 and micro-sized SiO2 particles. The IC50 value (50% concentration of inhibition) was associated with the size of SiO2 particles. Exposure to nano-SiO2 and micro-sized SiO2 particles also induced apoptosis in HaCaT cells in a dose-dependent manner. Furthermore, the smaller SiO2 particle size was, the higher apoptotic rate the cells underwent. The proteomic analysis revealed that 16 differentially expressed proteins were induced by SiO2 exposure, and that the expression levels of the differentially expressed proteins were associated with the particle size. The 16 proteins were identified by MALDI-TOF-TOF-MS analysis and could be classified into 5 categories according to their functions. They include oxidative stress-associated proteins; cytoskeleton-associated proteins; molecular chaperones; energy metabolism-associated proteins; apoptosis and tumor-associated proteins.
These results showed that nano-SiO2 exposure exerted toxic effects and altered protein expression in HaCaT cells. The data indicated the alterations of the proteins, such as the proteins associated with oxidative stress and apoptosis, could be involved in the toxic mechanisms of nano-SiO2 exposure.
纳米二氧化硅（nano-SiO2）在材料科学、工程和医学中有广泛的应用；然而，纳米 SiO2 暴露的潜在细胞生物学和蛋白质组学效应以及毒性机制仍远未明确。
在这里，我们通过生化和形态分析、二维差异凝胶电泳（2D-DIGE）和质谱（MS）评估了无定形纳米 SiO2（15nm、30nmSiO2）对 HaCaT 细胞活力、细胞周期、细胞凋亡和蛋白质表达的影响。我们发现，纳米 SiO2 和微米级 SiO2 颗粒处理后 HaCaT 细胞的细胞活力呈剂量依赖性显著下降。IC50 值（抑制的 50%浓度）与 SiO2 颗粒的大小有关。纳米 SiO2 和微米级 SiO2 颗粒暴露也会诱导 HaCaT 细胞凋亡，呈剂量依赖性。此外，SiO2 颗粒越小，细胞凋亡率越高。蛋白质组学分析显示，SiO2 暴露诱导了 16 种差异表达蛋白，并且差异表达蛋白的表达水平与颗粒大小有关。通过 MALDI-TOF-TOF-MS 分析鉴定了 16 个差异表达蛋白，根据其功能可分为 5 类。它们包括与氧化应激相关的蛋白；细胞骨架相关蛋白；分子伴侣；能量代谢相关蛋白；细胞凋亡和肿瘤相关蛋白。
这些结果表明，纳米 SiO2 暴露对 HaCaT 细胞产生了毒性作用并改变了蛋白质表达。数据表明，与氧化应激和细胞凋亡相关的蛋白质等蛋白质的改变可能参与了纳米 SiO2 暴露的毒性机制。
