Nrf2 deficiency exacerbates PM2.5-induced olfactory bulb injury
Nrf2 deficiency exacerbates PM2.5-induced olfactory bulb injury
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Nrf2 缺乏会加剧 PM2.5 引起的嗅球损伤
DOI：
10.1016/j.bbrc.2018.10.057
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发表时间：
2018-11-10
影响因子：
3.1
通讯作者：
Ding, Wenjun
中科院分区：
文献类型：
--
作者：
Chen, Xiaoyu;Liu, Shan;Ding, Wenjun
最近的研究表明，长期暴露于细颗粒物（PM2.5）会增加中枢神经（CNS）疾病的风险。核因子红细胞2相关因子2（nuclear factor erythroid 2-related factor 2，Nrf 2）是一种碱性亮氨酸拉链（basic region-leucine zipper，bZip）转录因子，在保护细胞免受化学诱导的氧化应激、恢复细胞氧化还原平衡中发挥重要作用。然而，Nrf 2对PM2.5神经毒性作用的影响仍有待了解。在这项研究中，我们通过鼻内滴注将野生型（WT）和Nrf 2敲除（Nrf 2（-/-））小鼠暴露于1 mg/kg PM2.5或去离子水28天。PM2.5暴露后，Nrf 2（-/-）小鼠的嗅球（OB）出现严重的神经损伤。在PM2.5处理的OB中，与WT小鼠的OB相比，Nrf 2缺乏导致抗氧化酶水平较低，氧化应激、小胶质细胞活化、炎症和核因子κ B（NF-κ B）活化的诱导更大。在PM2.5处理的BV 2细胞中，抑制Nrf 2活性显著降低细胞活力，增加细胞内活性氧（ROS）产生和核因子κ B（NF-κ B）磷酸化。总之，我们的研究结果提供了Nrf 2-reuglated的抗氧化剂和细胞保护酶在PM2.5诱导的神经毒性的保护反应中的作用。我们的研究结果表明，Nrf 2介导的抗氧化应激防御将有助于开发预防和治疗与空气污染相关疾病的新策略。(C)2018由Elsevier Inc.出版
Recent studies have demonstrated that long-term exposure to fine particulate matter (PM2.5) increases the risk of central nervous (CNS) diseases. As a basic region-leucine zipper (bZip) transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) is essential for protection against chemically induced oxidative stress to restore cellular redox balance. However, the impact of Nrf2 on the neurotoxic effects of PM2.5 remains to understand. In this study, we exposed wild-type (WT) and Nrf2 knockout (Nrf2(-/-)) mice to 1 mg/kg PM2.5 or deionized water by intranasal instillation for 28 days. After PM2.5 exposure, Nrf2(-/-) mice exhibited severe nerve injury in olfactory bulb (OB) of mice. In PM2.5-treated OBs, Nrf2 deficiency resulted in lower levels of antioxidant enzymes, greater induction of oxidative stress, microglia activation, inflammation and nuclear factor kappa B (NF-KB) activation compared to the OBs of WT mice. In PM2.5-treated BV2 cells, inhibition of Nrf2 activity significantly decreased cell viability and increased the intracellular reactive oxygen species (ROS) generation and nuclear factor kappa B (NF-KB) phosphorylation. Taken together, our results provide the role Nrf2-reuglated antioxidant and cytoprotective enzymes in protective responses to PM2.5-induced neurotoxicity. Our findings suggest Nrf2-mediated defenses against oxidative stress will help develop new strategies for the prevention and treatment of diseases associated with airborne pollution. (C) 2018 Published by Elsevier Inc.