NDLI: Critical Role of TAK1-Dependent Nuclear Factor-κB Signaling in 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced Astrocyte Activation and Subsequent Neuronal Death

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Critical Role of TAK1-Dependent Nuclear Factor-κB Signaling in 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced Astrocyte Activation and Subsequent Neuronal Death

Content Provider	Springer Nature Link
Author	Wan, Chunhua Zhang, Yang Jiang, Junkang Jiang, Shengyang Nie, Xiaoke Li, Aihong Guo, Aisong Wu, Qiyun
Copyright Year	2015
Abstract	2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been recently shown to elicit inflammatory response in a number of cell-types. However, whether TCDD could provoke inflammation in astrocytes, the most abundant glial cells in central nervous system (CNS), remains virtually unknown. In the present study, we showed that TCDD exposure could induce evident astrocyte activation both in vivo and in vitro. Further, we found that TGF-β-activated kinase 1 (TAK1), a critical regulator of NF-κB signaling, was rapidly phosphorylated in the process of TCDD-induced reactive astroglia. Exposure to TCDD led to rapid TAK1 and NF-κB p65 phosphorylation, as well as IKBα degradation. Moreover, blockage of TAK1 using siRNA oligos or TAK1 inhibitor 5Z-7-oxozeaenol significantly attenuated TCDD-induced astrocyte activation as well as the release of TNF-α. Finally, we showed that the conditioned medium of TCDD-treated astrocytes promoted the apoptosis of PC12 neuronal cells, which could be blocked with the pre-treatment of TAK1 inhibitor. Taken together, these findings suggested that TCDD could promote the inflammatory activation of astrocytes through modulating TAK1-NF-κB cascade, implicating that reactive astrocytes might contribute to TCDD-induced adverse effects on CNS system.
Starting Page	1220
Ending Page	1231
Page Count	12
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	40
Issue Number	6
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2015-05-22
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	TCDD TAK1 Activation Astrocytes NF-κB Neurosciences Neurochemistry Biochemistry Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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