Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure
Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure
复制标题
接触 PFOS 后，活性氧通过 HAPI 小胶质细胞中的 ERK/JNK MAPK 信号介导一氧化氮的产生。
DOI：
10.1016/j.taap.2015.06.012
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发表时间：
2015-10-15
影响因子：
3.8
通讯作者：
Wu, Qiyun
中科院分区：
文献类型：
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作者：
Wang, Cheng;Nie, Xiaoke;Wu, Qiyun
全氟辛烷磺酸(PFOS)是一种日常生活中常见的持久性污染物，已被证明对中枢神经系统(CNS)具有毒性作用。然而，全氟辛烷磺酸神经毒性的分子机制在很大程度上仍不清楚。高激活的小胶质细胞释放的炎性介质在各种神经系统疾病的发病机制中起着重要作用，这一点已得到广泛认可。在本研究中，我们研究了全氟辛烷磺酸暴露对小胶质细胞激活和促炎介质释放的影响，包括一氧化氮(NO)和活性氧化物种(ROS)。我们发现全氟辛烷磺酸可诱导大鼠肺小胶质细胞产生浓度依赖的NO和ROS。我们还发现，在全氟辛烷磺酸处理后的Hapi小胶质细胞中，ERK/JNK MAPK信号通路迅速激活。此外，PD98059和SP600125抑制ERK或JNK MAPK后，可抑制PFOS诱导的iNOS表达和NO的产生。有趣的是，ROS抑制剂NAC可以抑制iNOS的表达，NO的产生，以及ERK和JNK MAPKs的激活，这表明PFOS介导的小胶质细胞NO的产生是通过ROS/ERK/JNK MAPK信号通路发生的。最后，通过将SH-SY5Y细胞暴露于全氟辛烷磺酸处理的小胶质细胞条件培养液中，我们证明了NO在全氟辛烷磺酸介导的神经细胞凋亡中起作用。(C)2015 Elsevier Inc.保留所有权利。
Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis. (C) 2015 Elsevier Inc All rights reserved.