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Title: Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure

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 formore » 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.« less

Authors:
; ;  [1]; ;  [2];  [3]; ;  [2];  [3];  [1];  [1]
  1. Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China)
  2. Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China)
  3. Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China)
Publication Date:
OSTI Identifier:
22687775
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 288; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ABUNDANCE; APOPTOSIS; CENTRAL NERVOUS SYSTEM; CONCENTRATION RATIO; DISEASES; ECOLOGICAL CONCENTRATION; INFLAMMATION; INHIBITION; NITRIC OXIDE; OXIDATION; OXYGEN; PATHOGENESIS; RATS; SULFONATES; TOXICITY

Citation Formats

Wang, Cheng, Nie, Xiaoke, Zhang, Yan, Li, Ting, Mao, Jiamin, Liu, Xinhang, Gu, Yiyang, Shi, Jiyun, Xiao, Jing, Wan, Chunhua, and Wu, Qiyun. Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure. United States: N. p., 2015. Web. doi:10.1016/J.TAAP.2015.06.012.
Wang, Cheng, Nie, Xiaoke, Zhang, Yan, Li, Ting, Mao, Jiamin, Liu, Xinhang, Gu, Yiyang, Shi, Jiyun, Xiao, Jing, Wan, Chunhua, & Wu, Qiyun. Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure. United States. https://doi.org/10.1016/J.TAAP.2015.06.012
Wang, Cheng, Nie, Xiaoke, Zhang, Yan, Li, Ting, Mao, Jiamin, Liu, Xinhang, Gu, Yiyang, Shi, Jiyun, Xiao, Jing, Wan, Chunhua, and Wu, Qiyun. 2015. "Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure". United States. https://doi.org/10.1016/J.TAAP.2015.06.012.
@article{osti_22687775,
title = {Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure},
author = {Wang, Cheng and Nie, Xiaoke and Zhang, Yan and Li, Ting and Mao, Jiamin and Liu, Xinhang and Gu, Yiyang and Shi, Jiyun and Xiao, Jing and Wan, Chunhua and Wu, Qiyun},
abstractNote = {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.},
doi = {10.1016/J.TAAP.2015.06.012},
url = {https://www.osti.gov/biblio/22687775}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 288,
place = {United States},
year = {Thu Oct 15 00:00:00 EDT 2015},
month = {Thu Oct 15 00:00:00 EDT 2015}
}