ROS-mediated JNK pathway critically contributes to PFOS-triggered apoptosis in SH-SY5Y cells

Abstract

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.