PMID- 31775093
OWN - NLM
STAT- MEDLINE
DCOM- 20200904
LR  - 20200904
IS  - 1873-6750 (Electronic)
IS  - 0160-4120 (Linking)
VI  - 134
DP  - 2020 Jan
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin and up-regulation of neurofilament expression 
      in neuronal cells: Evaluation of AhR and MAPK pathways.
PG  - 105193
LID - S0160-4120(19)31290-5 [pii]
LID - 10.1016/j.envint.2019.105193 [doi]
AB  - Dioxin exposure is reported to affect nervous system development and increase the 
      risk of neurodegenerative diseases. Generally, dioxin exerts its neurotoxicity 
      via aryl hydrocarbon receptor (AhR). Neurofilament (NF) light (NFL) protein is a 
      biomarker for both neuronal differentiation and neurodegeneration and its 
      expression is controlled by the mitogen-activated protein kinase (MAPK) pathway. 
      However, the effects of dioxin on NFL expression and involved mechanisms are 
      incompletely understood. We aimed to investigate the effects of 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on NFL expression and elucidate the 
      underlining signaling pathways and their potential crosstalk, specifically 
      between MAPK and AhR pathway. We employed primary cultured rat cortical neurons 
      to evaluate the effect of TCDD exposure on NFL expression. We also used nerve 
      growth factor (NGF)-treated PC12 cells with specific inhibitors to investigate 
      the involvement of and potential crosstalk between the MAPK pathway and the AhR 
      pathway in mediating the effects of TCDD on NFL expression. After TCDD exposure, 
      NFL mRNA and protein levels were upregulated in cultured neurons. NFL protein was 
      preferentially found in the cell body compared with neurites of the cultured 
      neurons. In PC12 cells, TCDD enhanced both NGF-induced NFL expression and 
      phosphorylation of ERK1/2 and p38. The addition of MAPK-pathway inhibitors 
      (PD98059 and SB230580) partially blocked the TCDD-induced NFL upregulation. 
      CH223191, an AhR antagonist, reversed the upregulation of NFL and phosphorylation 
      of ERK1/2 and p38 induced by TCDD. This study demonstrated TCDD-induced 
      upregulation of NFL in cultured neurons, with protein retained in the cell body. 
      TCDD action was dependent on activation of AhR and MAPK, while crosstalk was 
      found between these two signaling pathways.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Chen, Yangsheng
AU  - Chen Y
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China; Institute of Environment and Health, Hangzhou Institute for 
      Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, 
      China; University of Chinese Academy of Sciences, Beijing 100085, China.
FAU - Xie, Heidi Qunhui
AU  - Xie HQ
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China; Institute of Environment and Health, Hangzhou Institute for 
      Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, 
      China; University of Chinese Academy of Sciences, Beijing 100085, China.
FAU - Sha, Rui
AU  - Sha R
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China; University of Chinese Academy of Sciences, Beijing 100085, China.
FAU - Xu, Tuan
AU  - Xu T
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China; University of Chinese Academy of Sciences, Beijing 100085, China.
FAU - Zhang, Songyan
AU  - Zhang S
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China; University of Chinese Academy of Sciences, Beijing 100085, China; 
      College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 
      518060, China.
FAU - Fu, Hualing
AU  - Fu H
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China; University of Chinese Academy of Sciences, Beijing 100085, China.
FAU - Xia, Yingjie
AU  - Xia Y
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China; University of Chinese Academy of Sciences, Beijing 100085, China.
FAU - Liu, Yiyun
AU  - Liu Y
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China; University of Chinese Academy of Sciences, Beijing 100085, China.
FAU - Xu, Li
AU  - Xu L
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China; Institute of Environment and Health, Hangzhou Institute for 
      Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, 
      China; University of Chinese Academy of Sciences, Beijing 100085, China. 
      Electronic address: lixu@rcees.ac.cn.
FAU - Zhao, Bin
AU  - Zhao B
AD  - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research 
      Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
      100085, China; Institute of Environment and Health, Hangzhou Institute for 
      Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, 
      China; University of Chinese Academy of Sciences, Beijing 100085, China. 
      Electronic address: binzhao@rcees.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191124
PL  - Netherlands
TA  - Environ Int
JT  - Environment international
JID - 7807270
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Intermediate Filaments
MH  - Mitogen-Activated Protein Kinases
MH  - Neurons
MH  - PC12 Cells
MH  - Polychlorinated Dibenzodioxins
MH  - Rats
MH  - Receptors, Aryl Hydrocarbon
MH  - Signal Transduction
MH  - *Up-Regulation
EDAT- 2019/11/28 06:00
MHDA- 2020/09/05 06:00
CRDT- 2019/11/28 06:00
PHST- 2019/06/05 00:00 [received]
PHST- 2019/08/25 00:00 [revised]
PHST- 2019/09/16 00:00 [accepted]
PHST- 2019/11/28 06:00 [pubmed]
PHST- 2020/09/05 06:00 [medline]
PHST- 2019/11/28 06:00 [entrez]
AID - S0160-4120(19)31290-5 [pii]
AID - 10.1016/j.envint.2019.105193 [doi]
PST - ppublish
SO  - Environ Int. 2020 Jan;134:105193. doi: 10.1016/j.envint.2019.105193. Epub 2019 
      Nov 24.