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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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.
author list (cited authors)
Legare, M. E., Hanneman, W. H., Barhoumi, R., & Tiffany-Castiglioni, E.
complete list of authors
Legare, ME||Hanneman, WH||Barhoumi, R||Tiffany-Castiglioni, E