The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure in primary rat astroglia: identification of biochemical and cellular targets.
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.
Legare
M E
ME
Departments of Veterinary Anatomy, Texas A&M University, College Station 77843, USA.
Hanneman
W H
WH
Barhoumi
R
R
Tiffany-Castiglioni
E
E
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists; D013329:Structure-Activity Relationship
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D005974:Glutamate-Ammonia Ligase; D002118:Calcium