School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, Singapore.
Toxicol Lett. 2011 Dec 15;207(3):213-21. doi: 10.1016/j.toxlet.2011.09.014. Epub 2011 Sep 21.
Graphitic nanomaterials are promising candidates for applications in electronics, energy, materials and biomedical areas. Nevertheless, few detailed studies related to the mechanistic understanding of these nanomaterials with the living systems have been performed to date. In the present study, our group applied the iTRAQ-coupled 2D LC-MS/MS approach to analyze the protein profile change of human hepatoma HepG2 cells treated with graphene and single-walled carbon nanotubes (SWCNTs), with the purpose of characterizing the interactions between living system and these nanomaterials at molecular level. Overall 37 differentially expressed proteins involved in metabolic pathway, redox regulation, cytoskeleton formation and cell growth were identified. Based on the protein profile, we found SWCNTs severely interfered the intracellular metabolic routes, protein synthesis and cytoskeletal systems. Moreover, our data suggested that SWCNTs might induce oxidative stress, thereby activating p53-mediated DNA damage checkpoint signals and leading to apoptosis. However, only moderate variation of protein levels for the cells treated with graphene was observed, which indicated graphene was less toxic and might be promising candidate for biomedical applications. We envision that this systematic characterization of cellular response at protein expression level will be of great importance to evaluate biocompatibility of nanomaterials.
石墨纳米材料在电子、能源、材料和生物医学等领域的应用具有广阔的前景。然而，迄今为止，很少有详细的研究涉及这些纳米材料与活体系统的机制理解。在本研究中，我们小组应用 iTRAQ 耦联 2D LC-MS/MS 方法分析了石墨烯和单壁碳纳米管（SWCNTs）处理人肝癌 HepG2 细胞的蛋白质谱变化，旨在从分子水平上表征活体系与这些纳米材料的相互作用。共鉴定到 37 种差异表达的蛋白质，涉及代谢途径、氧化还原调节、细胞骨架形成和细胞生长。基于蛋白质谱，我们发现 SWCNTs 严重干扰细胞内代谢途径、蛋白质合成和细胞骨架系统。此外，我们的数据表明，SWCNTs 可能诱导氧化应激，从而激活 p53 介导的 DNA 损伤检查点信号，导致细胞凋亡。然而，用石墨烯处理的细胞的蛋白质水平变化不大，这表明石墨烯的毒性较小，可能是生物医学应用的有前途的候选材料。我们设想，在蛋白质表达水平上对细胞反应进行系统的表征，对于评估纳米材料的生物相容性将是非常重要的。
