Nrf2 可防止二氧化硅纳米颗粒引起的氧化应激。
Nrf2 protects against oxidative stress induced by SiO nanoparticles.
机构信息
Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control & Prevention, Shenzhen 518055, China.
Medical School of Hunan Normal University, Changsha, 410013, China.
出版信息
Nanomedicine (Lond). 2017 Oct;12(19):2303-2318. doi: 10.2217/nnm-2017-0046. Epub 2017 Sep 19.
AIM
The aim of our study was to explore the role of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) on the exposure of SiO nanoparticles (NPs) and its influence.
MATERIALS & METHODS: To understand the mechanism of NP-induced oxidative stress, the involvement of oxidative-stress-responding transcription factors and the Nrf2/antioxidant reactive element (ARE) signaling pathway in the toxicity of SiO NPs' exposure was investigated via in vivo and in vitro models.
RESULTS
A549 cells showed a significant cytotoxic effect while A549-shNrf2 cells showed decreased cell viability after nm-SiO exposure. SiO NPs' exposure activated the Nrf2/ARE signaling pathway. Nrf2 exposed mice showed increased reactive oxygen species, 8-hydroxyl deoxyguanosine level and decreased total antioxidant capacity. Nrf2/ARE signaling pathway activation disrupted, leading inhibition of heme oxygenase-1 and upregulation of PKR-like endoplasmic-reticulum-regulated kinase.
CONCLUSION
Our findings suggested that Nrf2 could protect against oxidative stress induced by SiO NPs, and the Nrf2/ARE pathway might be involved in mild-to-moderate SiO NP-induced oxidative stress that was evident from dampened activity of Nrf2.
目的
本研究旨在探讨核因子红细胞 2(NF-E2)相关因子 2(Nrf2)在二氧化硅纳米颗粒(NPs)暴露及其影响中的作用。
材料与方法
为了了解 NP 诱导的氧化应激机制,通过体内和体外模型研究了氧化应激反应转录因子的参与和 Nrf2/抗氧化反应元件(ARE)信号通路在 SiO NPs 暴露毒性中的作用。
结果
nm-SiO 暴露后,A549 细胞表现出明显的细胞毒性作用,而 A549-shNrf2 细胞的细胞活力下降。SiO NPs 暴露激活了 Nrf2/ARE 信号通路。Nrf2 暴露小鼠表现出活性氧增加、8-羟基脱氧鸟苷水平升高和总抗氧化能力降低。Nrf2/ARE 信号通路的激活被破坏,导致血红素加氧酶-1 的抑制和 PKR 样内质网调节激酶的上调。
结论
我们的研究结果表明,Nrf2 可以保护细胞免受 SiO NPs 诱导的氧化应激,Nrf2/ARE 通路可能参与了轻度到中度的 SiO NP 诱导的氧化应激,这可以从 Nrf2 活性的减弱中得到证明。