百草枯通过提高细胞内 ROS 水平和抑制 Akt1 磷酸化来介导 BV-2 小胶质细胞的激活。
Paraquat mediates BV-2 microglia activation by raising intracellular ROS and inhibiting Akt1 phosphorylation.
机构信息
School of Public Health, MOE Key Laboratory of Public Health Safety, NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, 200032, China.
School of Public Health, MOE Key Laboratory of Public Health Safety, NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, 200032, China.
出版信息
Toxicol Lett. 2022 Feb 1;355:116-126. doi: 10.1016/j.toxlet.2021.11.017. Epub 2021 Dec 1.
Microglia is the innate immune cell in central nervous system (CNS) and plays an important role in neuroinflammation. Microglia mediated neuroinflammation is the key factor affecting the development of neurodegenerative diseases. Although there was evidence that paraquat (PQ) could induce inflammatory response, its mechanism was not clear. The present study investigated the mechanisms of PQ-induced inflammatory responses in BV-2 microglia cells, and tried to reveal the role of ROS/Akt1 pathway. The results showed that the cell activation markers (iNOS and CD206) of BV-2 cells were increased after PQ treatment, suggesting that BV-2 microglia were activated. PQ induced the reactive oxygen species (ROS) and inhibited the AKT1 phosphorylation in BV-2 cells. Besides, the M1 markers expression (IL-6, TNF-α and IL-1β) were significantly increased after PQ treatment, which suggested that PQ induced the increase of M1 phenotype of BV-2 microglia. Pre-treated with NAC (ROS scavenger), the M1 phenotype was decreased while the p-Akt1 was restored compared to PQ stimulation. Furthermore, we built an Akt1(S473E)-overexpression BV-2 cell line. The Akt1 (S473E) partially attenuated the PQ induced increase in M1 phenotype, while ROS did not significantly change. These results indicated that PQ induced BV-2 microglia activation by increased ROS mediated Akt1 activation inhibition, leading to neuroinflammation.
小胶质细胞是中枢神经系统（CNS）中的固有免疫细胞，在神经炎症中发挥重要作用。小胶质细胞介导的神经炎症是影响神经退行性疾病发展的关键因素。虽然有证据表明百草枯（PQ）可诱导炎症反应，但具体机制尚不清楚。本研究探讨了 PQ 诱导 BV-2 小胶质细胞炎症反应的机制，并试图揭示 ROS/Akt1 通路的作用。结果表明，PQ 处理后 BV-2 细胞的细胞激活标志物（iNOS 和 CD206）增加，表明 BV-2 小胶质细胞被激活。PQ 诱导 BV-2 细胞中活性氧（ROS）的产生并抑制 AKT1 磷酸化。此外，PQ 处理后 M1 标志物（IL-6、TNF-α和 IL-1β）的表达明显增加，表明 PQ 诱导 BV-2 小胶质细胞 M1 表型增加。与 PQ 刺激相比，用 NAC（ROS 清除剂）预处理后，M1 表型减少，而 p-Akt1 得到恢复。此外，我们构建了 Akt1（S473E）过表达 BV-2 细胞系。Akt1（S473E）部分减弱了 PQ 诱导的 M1 表型增加，而 ROS 没有明显变化。这些结果表明，PQ 通过增加 ROS 介导的 Akt1 激活抑制诱导 BV-2 小胶质细胞激活，导致神经炎症。
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