Department of Physiology, Department of Biomedical Sciences, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, 16499, Suwon, Republic of Korea.
College of Pharmacy, Sunchon National University, Suncheon, Republic of Korea.
Arch Toxicol. 2019 May;93(5):1201-1212. doi: 10.1007/s00204-019-02402-z. Epub 2019 Feb 8.
Nanoparticles are a useful material in biomedicine given their unique properties and biocompatibility; however, there is increasing concern regarding the potential toxicity of nanoparticles with respect to cell metabolism. Some evidence suggests that nanoparticles can disrupt glucose and energy homeostasis. In this study, we investigated the metabolomic, transcriptomic, and integrated effects of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO(RITC)] on glucose metabolism in human embryonic kidney 293 (HEK293) cells. Using gas chromatography-tandem mass spectrometry, we analysed the metabolite profiles of 14 organic acids (OAs), 20 amino acids (AAs), and 13 fatty acids (FAs) after treatment with 0.1 or 1.0 µg/µl MNPs@SiO(RITC) for 12 h. The metabolic changes were highly related to reactive oxygen species (ROS) generation and glucose metabolism. Additionally, effects on the combined metabolome and transcriptome or "metabotranscriptomic network" indicated a relationship between ROS generation and glucose metabolic dysfunction. In the experimental validation, MNPs@SiO(RITC) treatment significantly decreased the amount of glucose in cells and was associated with a reduction in glucose uptake efficiency. Decreased glucose uptake efficiency was also related to ROS generation and impaired glucose metabolism in the metabotranscriptomic network. Our results suggest that exposure to high concentrations of MNPs@SiO(RITC) produces maladaptive alterations in glucose metabolism and specifically glucose uptake as well as related metabolomic and transcriptomic disturbances via increased ROS generation. These findings further indicate that an integrated metabotranscriptomics approach provides useful and sensitive toxicological assessment for nanoparticles.
纳米粒子因其独特的性质和生物相容性在生物医药中是一种有用的材料；然而，人们越来越关注纳米粒子对细胞代谢的潜在毒性。有证据表明，纳米粒子可以破坏葡萄糖和能量稳态。在这项研究中，我们研究了含有罗丹明 B 异硫氰酸酯染料[MNPs@SiO（RITC）]的硅涂层磁性纳米粒子对人胚肾 293（HEK293）细胞葡萄糖代谢的代谢组学、转录组学和综合影响。使用气相色谱-串联质谱法，我们分析了 14 种有机酸（OAs）、20 种氨基酸（AAs）和 13 种脂肪酸（FAs）的代谢物谱，在 0.1 或 1.0μg/μl MNPs@SiO（RITC）处理 12 h 后。代谢变化与活性氧（ROS）的产生和葡萄糖代谢密切相关。此外，对组合代谢组学和转录组学或“代谢转录组网络”的影响表明 ROS 产生与葡萄糖代谢功能障碍之间存在关系。在实验验证中，MNPs@SiO（RITC）处理显著降低了细胞内的葡萄糖量，与葡萄糖摄取效率的降低有关。葡萄糖摄取效率的降低也与 ROS 产生和代谢转录组网络中葡萄糖代谢受损有关。我们的研究结果表明，暴露于高浓度的 MNPs@SiO（RITC）会导致葡萄糖代谢产生适应性改变，特别是葡萄糖摄取以及相关代谢组学和转录组学紊乱，这是通过增加 ROS 产生而引起的。这些发现进一步表明，整合的代谢转录组学方法为纳米粒子提供了有用和敏感的毒理学评估。
