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Author Wang, Cheng ♦ Nie, Xiaoke ♦ Zhang, Yan ♦ Li, Ting ♦ Mao, Jiamin ♦ Liu, Xinhang ♦ Gu, Yiyang ♦ Shi, Jiyun ♦ Xiao, Jing ♦ Wan, Chunhua ♦ Wu, Qiyun
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ABUNDANCE ♦ APOPTOSIS ♦ CENTRAL NERVOUS SYSTEM ♦ CONCENTRATION RATIO ♦ DISEASES ♦ ECOLOGICAL CONCENTRATION ♦ INFLAMMATION ♦ INHIBITION ♦ NITRIC OXIDE ♦ OXIDATION ♦ OXYGEN ♦ PATHOGENESIS ♦ RATS ♦ SULFONATES ♦ TOXICITY
Abstract Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis. - Highlights: • PFOS exposure induced expression of iNOS and production of NO in HAPI microglia. • PFOS induced the production of ROS in HAPI microglia. • ERK/JNK MAPK pathways were activated following PFOS exposure in HAPI microglia. • NO released by HAPI microglia participated in the apoptosis of SH-SY5Y cells.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-10-15
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 288
Issue Number 2


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