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• W1963529089 abstract "Perfluorohexanesulfonate (PFHxS) is one of the major perfluoroalkyl compounds (PFCs) found in human blood and its possible neurotoxicity has been suggested. However, the neuronal responses to PFHxS are not much known. Many studies have demonstrated that the early exposure to environmental chemicals increases the risk of neurodegenerative diseases such as Parkinson's disease in later life. In this study, the effects of PFHxS on the neuronal cell death and the underlying mechanisms were examined using PC12 cells as a model of dopaminergic neuron. The treatment with PFHxS reduced cell viability in a dose-dependent manner. PFHxS increased cell apoptosis which was measured by caspase-3 activity and TUNEL staining. MK801, a NMDA receptor antagonist reduced PFHxS-induced apoptosis. PFHxS increased the activations of ERK1/2, JNK and p38 MAPK with different temporal activations. The treatment with PD98059, an ERK inhibitor, significantly reduced apoptosis, whereas SB203580, a p38 MAPK inhibitor, had no effect. JNK inhibition by SP600125 significantly increased apoptosis. PFHxS exposure also increased ROS formation, which was completely blocked by antioxidants, Trolox or N-acetylcysteine (NAC). However, neither Trolox nor NAC reduced PFHxS-increased apoptosis, suggesting that ROS may not be a critical mediator for PFHxS-induced apoptosis of cells. Moreover, ERK activation induced by PFHxS was blocked by MK801 but not antioxidants. Taken together, these results have demonstrated that PFHxS induces the apoptosis of dopaminergic neuronal cells, where NMDA receptor-mediated ERK pathway plays a pro-apoptotic role and JNK plays an anti-apoptotic role. Our results may contribute to understanding cellular mechanisms for PFHxS-induced neurotoxicity." @default.
• W1963529089 created "2016-06-24" @default.
• W1963529089 creator A5046628656 @default.
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• W1963529089 date "2014-09-01" @default.
• W1963529089 modified "2023-10-02" @default.
• W1963529089 title "NMDA receptor-mediated ERK 1/2 pathway is involved in PFHxS-induced apoptosis of PC12 cells" @default.
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• W1963529089 doi "https://doi.org/10.1016/j.scitotenv.2014.01.114" @default.
• W1963529089 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24534200" @default.
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