Metabolic profiling reveals disorder of carbohydrate metabolism in mouse fibroblast cells induced by titanium dioxide nanoparticles
Metabolic profiling reveals disorder of carbohydrate metabolism in mouse fibroblast cells induced by titanium dioxide nanoparticles
复制标题
DOI：
10.1002/jat.2808
复制
发表时间：
2013-12-01
影响因子：
3.3
通讯作者：
Jia, Wei
中科院分区：
文献类型：
--
作者：
Jin, Chengyu;Liu, Yumin;Jia, Wei
随着二氧化钛（TiO 2）纳米颗粒在商业上的广泛应用，其潜在的生物安全性和代谢机制需要充分解释。在这项研究中，均匀和弱聚集（<100 nm）的二氧化钛纳米粒子的细胞毒性进行了研究，通过分析的代谢物谱的变化，在小鼠成纤维细胞（L929）和相应的培养基中使用气相色谱-飞行时间质谱（GC/TOFMS）为基础的代谢组学策略。多元统计分析表明，主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）模型分离效果较好。基于OPLS-DA模型中的变量重要性，通过比较TiO 2纳米颗粒处理的L929细胞或其相应的培养基与对照组，鉴定了一系列差异代谢物。研究发现，经TiO 2纳米颗粒处理的L929细胞及其相应培养基中的主要生化代谢（碳水化合物代谢）受到抑制。这些结果可能解释了TiO 2纳米颗粒诱导的L929细胞线粒体能量代谢严重受损和细胞氧化应激增加的原因。这些结果也表明，代谢组学策略在评估TiO 2纳米颗粒的细胞毒性方面具有很大的潜力，因此对于理解其潜在的分子机制非常有帮助。版权所有（c）2012约翰威利父子有限公司
As titanium dioxide (TiO2) nanoparticles are widely used commercially, their potential biosafety and metabolic mechanism needs to be fully explained. In this study, the cytotoxicity of homogeneous and weakly aggregated (< 100nm) TiO2 nanoparticles was investigated by analyzing the changes in metabolite profiles both in mouse fibroblast (L929) cells and their corresponding culture media using gas chromatograph with a time-of-flight mass spectrometry (GC/TOFMS)-based metabolomic strategy. With multivariate statistics analysis, satisfactory separations were observed in principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models. Based on the variable importance in the OPLS-DA models, a series of differential metabolites were identified by comparison between TiO2 nanoparticle-treated L929 cells or their corresponding culture media and the control groups. It was found that the major biochemical metabolism (carbohydrate metabolism) was suppressed in TiO2 nanoparticle-treated L929 cells and their corresponding culture media. These results might account for the serious damage to energy metabolism in mitochondria and the increased cellular oxidation stress in TiO2 nanoparticle-induced L929 cells. These results also suggest that the metabolomic strategy had a great potential in evaluating the cytotoxicity of TiO2 nanoparticles and thus was very helpful in understanding its underlying molecular mechanisms. Copyright (c) 2012 John Wiley & Sons, Ltd.