Effect of the SSeCKS–TRAF6 interaction on gastrodin-mediated protection against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced astrocyte activation and neuronal death
| Autor: | Yan Zhang, Tao Zhang, Qiyun Wu, Xinyuan Zhao, Changyue Wu, Man Jiao, Kaizhi Yin |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Polychlorinated Dibenzodioxins
Environmental Engineering Health Toxicology and Mutagenesis 0208 environmental biotechnology 02 engineering and technology 010501 environmental sciences Transfection 01 natural sciences Mice chemistry.chemical_compound Glucosides medicine Animals Environmental Chemistry heterocyclic compounds Viability assay Gastrodin Benzyl Alcohols 0105 earth and related environmental sciences Neurons Cell Death Glial fibrillary acidic protein biology NF-kappa B Public Health Environmental and Occupational Health Neurotoxicity NF-κB General Medicine General Chemistry medicine.disease Pollution 020801 environmental engineering Cell biology stomatognathic diseases medicine.anatomical_structure chemistry Apoptosis Astrocytes biology.protein Female Tumor necrosis factor alpha Astrocyte |
| Zdroj: | Chemosphere. 226:678-686 |
| ISSN: | 0045-6535 |
| DOI: | 10.1016/j.chemosphere.2019.04.003 |
| Popis: | The ubiquitous environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to trigger neurotoxicity. In this study, we investigated the protective effects of gastrodin on TCDD-induced neurotoxicity and the underlying molecular mechanisms. The results show that gastrodin decreased cell viability, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release, and inducible nitrix oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) expression in TCDD-treated C6 cells. TCDD stimulated NF-κB signalling activation, demonstrated by increased p-NF-κB expression and translocation of nuclear Factor kappa B (NF-κB) to the nucleus. TCDD did not affect TRAF6 protein expression but enhanced the attenuated the Src-suppressed-C Kinase Substrate (SSeCKS)–tumor necrosis factor receptor-associated factor 6 (TRAF6) interaction, thereby triggering NF-κB signalling activation. Gastrodin inhibited TCDD-induced NF-κB signalling activation by lessening the SSeCKS–TRAF6 interaction in vitro. Gastrodin attenuated SSeCKS–TRAF6 interaction in vivo and protected mice from NF-κB signalling activation following TCDD exposure. Finally, gastrodin blocked the apoptosis of PC12 neuronal cells induced by medium conditioned with TCDD-treated astrocytes. In summary, gastrodin inhibited TCDD-induced NF-κB signalling activation by lessening the SSeCKS–TRAF6 interaction, resulting in attenuated astrocyte activation and subsequent neuronal apoptosis. These findings will contribute to an improved understanding of TCDD-induced neurotoxicity and strategies to antagonise it using gastrodin. |
| Databáze: | OpenAIRE |
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