Legare M E, Hanneman W H, Barhoumi R, Tiffany-Castiglioni E
Departments of Veterinary Anatomy, Texas A&M University, College Station 77843, USA.
Neurotoxicology. 1997;18(2):515-24.
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.
本文报告了利用活体荧光探针和生化分析进行体外实验的结果，以研究2,3,7,8-四氯二苯并对二恶英（2,3,7,8-TCDD）及相关化合物对原代大鼠星形胶质细胞的影响，从而确定毒性作用涉及的细胞部位。应用100 nM 2,3,7,8-TCDD（一种强效芳烃受体激动剂）导致星形胶质细胞内钙离子改变、谷胱甘肽显著减少、线粒体膜电位破坏、谷氨酰胺合成酶免疫反应性显著降低以及最终pH维持能力丧失。相比之下，应用10 μM 1,2,3,4-TCDD（一种弱芳烃受体激动剂）对所测的任何参数均无影响。这些发现，再加上在培养的大鼠星形胶质细胞中鉴定出9-10S胞质芳烃受体，与其他芳烃受体介导的反应所观察到的典型构效关系一致。然而，本研究中观察到的钙离子变化的时间进程以及其他反应表明，上述效应不一定涉及核芳烃受体复合物的形成。
