Physiatry Department, The Second People's Hospital of Nan Tong, Nantong, Jiangsu 226001, People's Republic of China.
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Environ Toxicol Pharmacol. 2016 Sep;46:9-16. doi: 10.1016/j.etap.2016.06.025. Epub 2016 Jun 27.
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.
全氟辛烷磺酸（PFOS）是目前研究最多的全氟烷基和多氟烷基物质（PFASs）之一，被认为对哺乳动物的中枢神经系统（CNS）有毒。然而，PFOS 的神经毒性作用在很大程度上仍然未知。在这项研究中，研究了 PFOS 对小胶质细胞凋亡的影响。结果表明，PFOS 可显著降低 HAPI 小胶质细胞的细胞活力并介导细胞凋亡，这与 ROS 产生和 p53 过表达密切相关。此外，p53 干扰可显著改善 HAPI 小胶质细胞中 PFOS 引发的细胞毒性作用，包括下调 cleaved PARP 和 cleaved caspase 3。有趣的是，ROS 抑制剂 NAC 抑制了 p53 的表达，并减少了 HAPI 小胶质细胞的凋亡。综上所述，这些发现表明，ROS 的过度产生通过调节 p53 信号通路在 PFOS 介导的 HAPI 小胶质细胞凋亡中发挥重要作用。
