Recent studies have indicated that perfluorooctane sulfonate (PFOS) and its derivatives can lead to neurotoxicity. In the present study, we showed that PFOS may trigger neuronal apoptosis through a c-Jun N-terminal kinase (JNK)-related mechanism. We revealed that c-Jun N-terminal kinase (JNK) was robustly activated in PFOS-exposed neuronal cells. The doses of PFOS that initiates JNK activation coincides with that inducing neuronal apoptosis, as confirmed by western blot and Annexin V-PE/7-AAD analyses. In addition, we found that reactive oxidative species (ROS) accumulation plays a casual role in PFOS-initiated JNK activation, as treatment with ROS scavenger N-acetyl-l-cysteine (NAC) abrogated PFOS-induced mitochondrial and nuclear translocation of phosphorylated JNK (p-JNK). In keeping with this notion, the expression of JNK downstream pro-apoptotic target Bim was increased following PFOS exposure in JNK- and ROS-dependent manners. Finally, Annexin V-PE/7-AAD analysis uncovered that treatment with NAC or SP600125 could significantly impair PFOS-induced neuronal apoptosis. These findings implicate that JNK signaling is critically involved in PFOS-induced neuronal death by virtue of mitochondrial translocation and the transcription of pro-apoptotic genes.

中文翻译：

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ROS介导的JNK通路在促成PFOS触发的SH-SY5Y细胞凋亡中起关键作用。

最近的研究表明，全氟辛烷磺酸盐（PFOS）及其衍生物可导致神经毒性。在本研究中，我们表明PFOS可能通过c-Jun N端激酶（JNK）相关机制触发神经元凋亡。我们揭示了c-Jun N端激酶（JNK）在暴露于PFOS的神经元细胞中被强烈激活。Western blot和Annexin V-PE / 7-AAD分析证实，引发JNK活化的PFOS剂量与诱导神经元凋亡的剂量一致。此外，我们发现活性氧化物质（ROS）积累在PFOS引发的JNK活化中起着偶然的作用，因为用ROS清除剂N-乙酰基-1-半胱氨酸（NAC）消除了PFOS诱导的线粒体和磷酸化JNK的核易位（p-JNK）。按照这个观念，全氟辛烷磺酸暴露后，JNK和ROS依赖性方式增加JNK下游促凋亡靶标Bim的表达。最后，Annexin V-PE / 7-AAD分析发现，NAC或SP600125的治疗可显着削弱PFOS诱导的神经元凋亡。这些发现暗示JNK信号传导由于线粒体易位和促凋亡基因的转录而与PFOS诱导的神经元死亡至关重要。