Neuronal activity enhances aryl hydrocarbon receptor-mediated gene expression and dioxin neurotoxicity in cortical neurons

Chun Hua Lin, Shu Hui Juan, Chen Yu Wang, Yu Yo Sun, Chih Ming Chou, Shwu Fen Chang, Ssu Yao Hu, Wen Sen Lee, Yi-Hsuan Lee

研究成果: 雜誌貢獻文章

36 引文 (Scopus)

摘要

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor activated by dioxin and polyaromatic hydrocarbons. Recent studies have revealed that AhR activity in central neurons depends on the NMDA receptor. In this study, we investigated how the neuronal activity influence AhR-mediated dioxin-responsive gene expression and neurotoxicity. Our results show that activation of AhR by the selective agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin induced dioxin-responsive gene expression and calcium entry, which were attenuated by AhR small interfering RNA, the NMDA receptor channel blocker MK801, and the action potential blocker tetrodotoxin (TTX). In addition, AhR-mediated gene expression was enhanced in neurons during synaptogenesis (10 days in vitro) compared with younger neurons (4 days in vitro), as was sensitivity to TTX and MK801. Furthermore, TTX and MK801 differentially affected the association of AhR and its transcriptional co-activator cAMP-responsive-element binding protein with the cytochrome P450 1A1 (cyp1A1) gene enhancer. Calcium/calmodulin-dependent protein kinase IV, the cAMP-responsive-element binding protein activating enzyme, was also activated by 2,3,7,8-tetrachlorodibenzo-p-dioxin in an activity-dependent manner. Finally, we found that neuronal susceptibility to dioxin insult was also maturation and activity-dependent. Together, the results suggest that neuronal activity may facilitate AhR-mediated calcium signaling, which in turn enhances AhR-mediated gene regulation and mediated maturation-dependent dioxin neurotoxicity.
原文英語
頁(從 - 到)1415-1429
頁數15
期刊Journal of Neurochemistry
104
發行號5
DOIs
出版狀態已發佈 - 三月 2008

指紋

Aryl Hydrocarbon Receptors
Dioxins
Gene expression
Neurons
Gene Expression
Tetrodotoxin
N-Methyl-D-Aspartate Receptors
Carrier Proteins
Calcium-Calmodulin-Dependent Protein Kinase Type 4
Calcium
Calcium Signaling
Hydrocarbons
Cytochrome P-450 Enzyme System
Small Interfering RNA
Genes
Action Potentials
Transcription Factors
Chemical activation
Association reactions
Ligands

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

引用此文

Neuronal activity enhances aryl hydrocarbon receptor-mediated gene expression and dioxin neurotoxicity in cortical neurons. / Lin, Chun Hua; Juan, Shu Hui; Wang, Chen Yu; Sun, Yu Yo; Chou, Chih Ming; Chang, Shwu Fen; Hu, Ssu Yao; Lee, Wen Sen; Lee, Yi-Hsuan.

於: Journal of Neurochemistry, 卷 104, 編號 5, 03.2008, p. 1415-1429.

研究成果: 雜誌貢獻文章

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abstract = "The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor activated by dioxin and polyaromatic hydrocarbons. Recent studies have revealed that AhR activity in central neurons depends on the NMDA receptor. In this study, we investigated how the neuronal activity influence AhR-mediated dioxin-responsive gene expression and neurotoxicity. Our results show that activation of AhR by the selective agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin induced dioxin-responsive gene expression and calcium entry, which were attenuated by AhR small interfering RNA, the NMDA receptor channel blocker MK801, and the action potential blocker tetrodotoxin (TTX). In addition, AhR-mediated gene expression was enhanced in neurons during synaptogenesis (10 days in vitro) compared with younger neurons (4 days in vitro), as was sensitivity to TTX and MK801. Furthermore, TTX and MK801 differentially affected the association of AhR and its transcriptional co-activator cAMP-responsive-element binding protein with the cytochrome P450 1A1 (cyp1A1) gene enhancer. Calcium/calmodulin-dependent protein kinase IV, the cAMP-responsive-element binding protein activating enzyme, was also activated by 2,3,7,8-tetrachlorodibenzo-p-dioxin in an activity-dependent manner. Finally, we found that neuronal susceptibility to dioxin insult was also maturation and activity-dependent. Together, the results suggest that neuronal activity may facilitate AhR-mediated calcium signaling, which in turn enhances AhR-mediated gene regulation and mediated maturation-dependent dioxin neurotoxicity.",
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AU - Lin, Chun Hua

AU - Juan, Shu Hui

AU - Wang, Chen Yu

AU - Sun, Yu Yo

AU - Chou, Chih Ming

AU - Chang, Shwu Fen

AU - Hu, Ssu Yao

AU - Lee, Wen Sen

AU - Lee, Yi-Hsuan

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N2 - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor activated by dioxin and polyaromatic hydrocarbons. Recent studies have revealed that AhR activity in central neurons depends on the NMDA receptor. In this study, we investigated how the neuronal activity influence AhR-mediated dioxin-responsive gene expression and neurotoxicity. Our results show that activation of AhR by the selective agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin induced dioxin-responsive gene expression and calcium entry, which were attenuated by AhR small interfering RNA, the NMDA receptor channel blocker MK801, and the action potential blocker tetrodotoxin (TTX). In addition, AhR-mediated gene expression was enhanced in neurons during synaptogenesis (10 days in vitro) compared with younger neurons (4 days in vitro), as was sensitivity to TTX and MK801. Furthermore, TTX and MK801 differentially affected the association of AhR and its transcriptional co-activator cAMP-responsive-element binding protein with the cytochrome P450 1A1 (cyp1A1) gene enhancer. Calcium/calmodulin-dependent protein kinase IV, the cAMP-responsive-element binding protein activating enzyme, was also activated by 2,3,7,8-tetrachlorodibenzo-p-dioxin in an activity-dependent manner. Finally, we found that neuronal susceptibility to dioxin insult was also maturation and activity-dependent. Together, the results suggest that neuronal activity may facilitate AhR-mediated calcium signaling, which in turn enhances AhR-mediated gene regulation and mediated maturation-dependent dioxin neurotoxicity.

AB - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor activated by dioxin and polyaromatic hydrocarbons. Recent studies have revealed that AhR activity in central neurons depends on the NMDA receptor. In this study, we investigated how the neuronal activity influence AhR-mediated dioxin-responsive gene expression and neurotoxicity. Our results show that activation of AhR by the selective agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin induced dioxin-responsive gene expression and calcium entry, which were attenuated by AhR small interfering RNA, the NMDA receptor channel blocker MK801, and the action potential blocker tetrodotoxin (TTX). In addition, AhR-mediated gene expression was enhanced in neurons during synaptogenesis (10 days in vitro) compared with younger neurons (4 days in vitro), as was sensitivity to TTX and MK801. Furthermore, TTX and MK801 differentially affected the association of AhR and its transcriptional co-activator cAMP-responsive-element binding protein with the cytochrome P450 1A1 (cyp1A1) gene enhancer. Calcium/calmodulin-dependent protein kinase IV, the cAMP-responsive-element binding protein activating enzyme, was also activated by 2,3,7,8-tetrachlorodibenzo-p-dioxin in an activity-dependent manner. Finally, we found that neuronal susceptibility to dioxin insult was also maturation and activity-dependent. Together, the results suggest that neuronal activity may facilitate AhR-mediated calcium signaling, which in turn enhances AhR-mediated gene regulation and mediated maturation-dependent dioxin neurotoxicity.

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KW - Neuronal survival

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