2,3,7,8-tetrachlorodibenzo-p-dioxin exposure influence the expression of glutamate transporter GLT-1 in C6 glioma cells via the Ca2+/protein kinase C pathway
2,3,7,8-tetrachlorodibenzo-p-dioxin exposure influence the expression of glutamate transporter GLT-1 in C6 glioma cells via the Ca2+/protein kinase C pathway
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2,3,7,8-四氯二苯并-对二恶英暴露通过 Ca2/蛋白激酶 C 途径影响 C6 胶质瘤细胞中谷氨酸转运蛋白 GLT-1 的表达
DOI：
10.1002/jat.3294
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发表时间：
2016
影响因子：
3.3
通讯作者：
Wu Qiyun
中科院分区：
文献类型：
--
作者：
Zhao Jianya;Zhang Yan;Zhao Jianmei;Wang Cheng;Mao Jiamin;Li Ting;Wang Xiaoke;Nie Xiaoke;Jiang Shengyang;Wu Qiyun
广泛存在的环境污染物2，3，7，8-四氯二苯并对二恶英（TCDD）被认为是毒性最大的二恶英类化合物之一。虽然流行病学研究表明，TCDD暴露与一些神经和神经生理疾病有关，但TCDD介导的神经毒性的潜在机制仍不清楚。星形胶质细胞是神经系统中数量最多的细胞，被认为是正常脑功能以及神经系统、神经发育和神经退行性脑疾病的重要介质。在这项研究中，我们研究了TCDD在调节星形胶质细胞谷氨酸转运蛋白GLT-1表达中的作用。浓度为0.1 ~ 100 nm的TCDD对C6胶质瘤细胞的存活率无明显影响。然而，GLT-1在C6胶质瘤细胞中的表达以剂量和时间依赖性方式下调。TCDD还引起蛋白激酶C（PKC）的激活，因为TCDD诱导PKC从细胞质或核周易位到膜。PKC的转位被一种钙离子阻断剂硝苯地平抑制，这表明该效应是由初始升高的细胞内游离钙离子浓度触发的。最后，我们发现抑制PKC活性可以逆转TCDD触发的GLT-1减少。综上所述，我们的研究结果表明，TCDD暴露可通过Ca 2 +/PKC途径下调C6细胞GLT-1的表达。GLT-1的下调可能参与了TCDD介导的神经毒性。版权所有© 2016约翰威利父子有限公司.
The widespread environmental contaminant, 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD), is considered one of the most toxic dioxin‐like compounds. Although epidemiological studies have shown that TCDD exposure is linked to some neurological and neurophysiological disorders, the underlying mechanism of TCDD‐mediated neurotoxicity has remained unclear. Astrocytes are the most abundant cells in the nervous systems, and are recognized as the important mediators of normal brain functions as well as neurological, neurodevelopmental and neurodegenerative brain diseases. In this study, we investigated the role of TCDD in regulating the expression of glutamate transporter GLT‐1 in astrocytes. TCDD, at concentrations of 0.1–100 nm, had no significantly harmful effect on the viability of C6 glioma cells. However, the expression of GLT‐1 in C6 glioma cells was downregulated in a dose‐ and time‐dependent manner. TCDD also caused activation of protein kinase C (PKC), as TCDD induced translocation of the PKC from the cytoplasm or perinuclear to the membrane. The translocation of PKC was inhibited by one Ca2+blocker, nifedipine, suggesting that the effects are triggered by the initial elevated intracellular concentration of free Ca2+. Finally, we showed that inhibition of the PKC activity reverses the TCDD‐triggered reduction of GLT‐1. In summary, our results suggested that TCDD exposure could downregulate the expression of GLT‐1 in C6 via Ca2+/PKC pathway. The downregulation of GLT‐1 might participate in TCDD‐mediated neurotoxicity. Copyright © 2016 John Wiley & Sons, Ltd.