SOD1 overexpression alters ROS production and reduces neurotoxic inflammatory signaling in microglial cells
SOD1 overexpression alters ROS production and reduces neurotoxic inflammatory signaling in microglial cells
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DOI：
10.1016/j.jneuroim.2006.10.003
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Bruce-Keller, Amadora J.
中科院分区：
文献类型：
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作者：
Dimayuga, Filomena O.;Wang, Chunmei;Bruce-Keller, Amadora J.
氧化爆发的激活是小胶质细胞激活中最早的生化事件之一，但目前还不清楚自由基如何参与炎症信号。为了确定特定的活性氧物种在小胶质细胞激活中所起的作用，我们在N9小鼠的小胶质细胞中操纵了SOD1的水平。SOD1的稳定过表达导致超氧化物和一氧化氮的产生显著减少，同时在脂多糖诱导下过氧化氢的产生增加。然而，在SOD1过表达的细胞中，内毒素诱导的核因子kappaB的激活以及肿瘤坏死因子α和IL-6的释放明显减弱，小胶质细胞对培养神经元的毒性也明显减弱。相反，用双硫仑急性抑制SOD1与增加一氧化氮和细胞因子的释放以及增加神经毒性有关。综上所述，这些数据表明，小胶质细胞中的超氧阴离子自由基在引导氧化还原敏感型炎症信号和启动神经毒性炎症中发挥重要作用。(C)2006爱思唯尔B.V.保留所有权利。
Activation of the oxidative burst is one of the earliest biochemical events in microglial activation, but it is not understood yet how free radicals participate in inflammatory signaling. To determine the role that specific reactive oxygen species play in microglial activation, the levels of SOD1 were manipulated in N9 murine microglia. Stable overexpression of SOD1 caused significant decreases in superoxide and nitric oxide production, with concurrent increases in hydrogen peroxide following LPS. However, LPS-induced activation of NF kappa B, and release of TNF alpha and IL-6 were significantly attenuated in SOD1 overexpressing cells, as was the ability of microglia to induce toxicity in cultured neurons. Conversely, acute inhibition of SOD1 with disulfiram was associated with increased nitric oxide and cytokine release, and increased neurotoxicity. Together, these data suggest that superoxide radicals in microglia, play important roles in directing redox-sensitive inflammatory signaling and initiating neurotoxic inflammation. (c) 2006 Elsevier B.V All rights reserved.