Department of Neurology, Zengcheng District People's Hospital of Guangzhou, Guangzhou, China.
Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Oxid Med Cell Longev. 2019 Mar 13;2019:2601394. doi: 10.1155/2019/2601394. eCollection 2019.
Oxidative stress plays an important role in various neurological disorders. Milk fat globule-epidermal growth factor-factor 8 (MFG-E8) is a regulatory protein for microglia. However, its involvement in microglial oxidative stress has not been established. In this study, we observed microglial oxidative stress in response to lipopolysaccharide (LPS) both and . LPS induced significant elevation of TNF-, IL-6, MDA, and ROS and reduction of GSH and SOD in the mouse brains and primary microglia, which were reversed by MFG-E8 pretreatment. MFG-E8 induced the expression of Nrf-2 and HO-1 that was reduced by LPS incubation. Moreover, LPS-increased Keap-1 expression was reversed by MFG-E8. But the above tendencies were not seen when MFG-E8 was applied alone. The current study established the involvement of MFG-E8 in antioxidant effects during neuroinflammation. It may achieve the effects through the regulation of Keap-1/Nrf-2/HO-1 pathways.
氧化应激在各种神经紊乱中起着重要作用。牛奶脂肪球-表皮生长因子因子 8（MFG-E8）是小胶质细胞的调节蛋白。然而，其是否参与小胶质细胞氧化应激尚未确定。在这项研究中，我们观察到脂多糖（LPS）刺激下的小胶质细胞氧化应激，结果发现 LPS 诱导了小鼠大脑和原代小胶质细胞中 TNF-α、IL-6、MDA 和 ROS 的显著升高，以及 GSH 和 SOD 的降低，而 MFG-E8 预处理则逆转了这种情况。MFG-E8 诱导了 Nrf-2 和 HO-1 的表达，而 LPS 孵育则降低了这种表达。此外，LPS 诱导的 Keap-1 表达增加也被 MFG-E8 逆转。但是，当单独应用 MFG-E8 时，并没有出现上述趋势。本研究确立了 MFG-E8 在神经炎症期间的抗氧化作用，它可能通过调节 Keap-1/Nrf-2/HO-1 通路来实现这些作用。
