ROS-mediated apoptosis of HAPI microglia through p53 signaling following PFOS exposure
ROS-mediated apoptosis of HAPI microglia through p53 signaling following PFOS exposure
复制标题
PFOS 暴露后，ROS 通过 p53 信号传导 HAPI 小胶质细胞凋亡
DOI：
10.1016/j.etap.2016.06.025
复制
发表时间：
2016-09-01
影响因子：
4.3
通讯作者：
Wu, Qiyun
中科院分区：
文献类型：
--
作者：
Ge, Jianbin;Wang, Cheng;Wu, Qiyun
全氟辛烷磺酸 (PFOS) 是全氟烷基和多氟烷基物质 (PFAS) 中研究最广泛的成员，被认为对哺乳动物的中枢神经系统 (CNS) 有毒。然而，全氟辛烷磺酸的神经毒性作用仍然很大程度上未知。在本研究中，检测了 PFOS 对小胶质细胞凋亡的影响。结果表明，PFOS能够显着降低HAPI小胶质细胞的细胞活力并介导细胞凋亡，这与ROS的产生和p53的过度表达密切相关。此外，p53干扰显着改善了PFOS在HAPI小胶质细胞中引发的细胞毒性作用，包括下调裂解的PARP和裂解的caspase 3。有趣的是，ROS抑制剂NAC抑制p53表达，并减少HAPI小胶质细胞的凋亡。总而言之，这些发现表明，ROS 产生的上调通过 p53 信号传导的调节，在 PFOS 介导的 HAPI 小胶质细胞细胞凋亡中发挥着至关重要的作用。 (C) 2016 Elsevier B.V. 保留所有权利。
Perfluorooctane sulfonate (PFOS), the most extensively studied member of perfluoroalkyl and polyfluoroalkyl substances (PFASs), has been thought to be toxic to the central nervous system (CNS) of mammals. However, the neurotoxic effects of PFOS remain largely unknown. In this study, the effect of PFOS on microglial apoptosis was examined. The results showed that PFOS could significantly reduce the cell viability and mediate cell apoptosis in HAPI microglia, which was closely accompanied with ROS production and p53 overexpression. Moreover, p53 interference significantly ameliorated PFOS-triggered cytotoxic effects in HAPI microglia, including the downregulation of cleaved PARP and cleaved caspase 3. Interestingly, NAC, a ROS inhibitor, inhibited p53 expression, and decreased the apoptosis of HAPI microglia. Taken together, these findings suggest that upregulated production of ROS plays a vital role in PFOS-mediated apoptosis in HAPI microglia via the modulation of p53 signaling. (C) 2016 Elsevier B.V. All rights reserved.