a Key Laboratory of Environmental Medicine Engineering in Ministry of Education , Medical School, Southeast University , Nanjing , China.
Nanotoxicology. 2017 May;11(4):578-590. doi: 10.1080/17435390.2017.1329954. Epub 2017 May 19.
Upon exposure to environmental engineered nanomaterials (ENMs), animals will activate certain response signals to protect themselves from the toxic effects. However, the underlying molecular mechanisms for this response are still largely unclear. Using in vivo assay system of Caenorhabditis elegans, we here found that antimicrobial proteins of LYS-1, LYS-8, SPP-1, DOD-6, and F55G11.4 were activated by graphene oxide (GO) exposure. These antimicrobial proteins functioned as molecular targets of transcriptional factor DAF-16 in insulin signaling pathway, and acted in intestine to regulate the response to GO. Among these antimicrobial proteins, DOD-6, F55G11.4, and SPP-1 participated in the formation of signaling cascade of DAF-16-DOD-6-SOD-3-F55G11.4/SPP-1 in response to GO exposure by activating the antioxidation system. Different from this, LYS-1 and LYS-8, two lysozymes, mediated TUB-2 signaling and DAF-8-DAF-5 signaling cascade, respectively, to regulate the response to GO exposure. During the regulation of response to GO exposure, LYS-1 and LYS-8 acted synergistically, which could be largely explained by the observed synergistic interaction between TUB-2 and DAF-8. Therefore, our results demonstrate the crucial protection role of antimicrobial proteins for animals in response to environmental ENMs' exposure. The elucidated different signaling cascades mediated by antimicrobial proteins provide important molecular targets for future toxicity assessment and chemical modification of GO.
动物在接触环境工程纳米材料(ENMs)时,会激活某些反应信号来保护自己免受毒性影响。然而,这种反应的潜在分子机制在很大程度上仍不清楚。我们使用秀丽隐杆线虫的体内检测系统,发现了抗菌蛋白 LYS-1、LYS-8、SPP-1、DOD-6 和 F55G11.4 会因氧化石墨烯(GO)暴露而被激活。这些抗菌蛋白作为胰岛素信号通路中转录因子 DAF-16 的分子靶标,在肠道中发挥作用,调节对 GO 的反应。在这些抗菌蛋白中,DOD-6、F55G11.4 和 SPP-1 通过激活抗氧化系统,参与 DAF-16-DOD-6-SOD-3-F55G11.4/SPP-1 信号级联的形成,以响应 GO 暴露。与此不同的是,两种溶菌酶 LYS-1 和 LYS-8 分别介导 TUB-2 信号和 DAF-8-DAF-5 信号级联,以调节对 GO 暴露的反应。在调节对 GO 暴露的反应过程中,LYS-1 和 LYS-8 表现出协同作用,这可以从观察到的 TUB-2 和 DAF-8 之间的协同相互作用得到很大程度的解释。因此,我们的研究结果表明,抗菌蛋白在动物应对环境 ENMs 暴露时发挥着至关重要的保护作用。阐明抗菌蛋白介导的不同信号级联为未来对 GO 的毒性评估和化学修饰提供了重要的分子靶标。