The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure in primary rat astroglia: identification of biochemical and cellular targets.
The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure in primary rat astroglia: identification of biochemical and cellular targets.
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发表时间：
1997
期刊：
影响因子：
3.4
通讯作者：
M. Légaré;W. Hanneman;R. Barhoumi;E. Tiffany‐Castiglioni
中科院分区：
文献类型：
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作者：
M. Légaré;W. Hanneman;R. Barhoumi;E. Tiffany‐Castiglioni
本文报道了利用荧光探针和生物化学方法研究2,3,7,8-四氯二苯并-对二恶英（2,3,7,8- tcdd）及其相关化合物对大鼠初代星形胶质细胞毒性作用的体外实验结果，以确定参与毒性的细胞部位。应用100 nM 2,3,7,8- tcdd（一种强Ah受体激动剂）导致星形胶质细胞内Ca2+改变，谷胱甘肽显著降低，线粒体膜电位破坏，谷氨酰胺合成酶免疫反应性显著降低，最终失去pH维持。相比之下，应用10微米1,2,3,4- tcdd（一种弱Ah受体激动剂）对任何测量参数都没有影响。这些发现，再加上培养大鼠星形胶质细胞中9-10S胞质Ah受体的鉴定，与其他Ah受体介导的反应中观察到的典型结构-活性关系一致。然而，Ca2+的时间过程以及本研究中观察到的其他反应表明，上述效应可能不一定涉及核Ah受体复合物的形成。
This paper reports the results from in vitro experiments utilizing vital fluorescent probes and biochemical assays to examine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and related compounds in primary rat astroglia in an effort to identify the cellular site(s) involved in toxicity. Application of 100 nM 2,3,7,8-TCDD, a strong Ah receptor agonist, resulted in altered astroglial intracellular Ca2+, a significant decrease in glutathione, a disrupted mitochondrial membrane potential, a significant decrease in glutamine synthetase immunoreactivity and eventual loss of pH maintenance. In contrast, application of 10 microM 1,2,3,4-TCDD, a weak Ah receptor agonist, had no effect on any parameters measured. These findings, coupled with the identification of the 9-10S cytosolic Ah receptor in cultured rat astroglia, are consistent with typical structure-activity relationships observed for other Ah receptor mediated responses. However, the time course of the Ca2+, as well as other responses observed in this study, suggest that the above effects may not necessarily involved the formation of the nuclear Ah receptor complex.