Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 392, Issue 1-2, Pages 90-105Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2014.05.008
Keywords
GSK-3 beta; Bcl-2; Caspases; Estrogen receptors; Neurotoxicity; Primary neuronal cell cultures
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Funding
- Operating Program of Innovative Economy [POIG.01.01.02-12-004/09]
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Extended residual persistence of the pesticide dichlorodiphenyltrichloroethane (DDT) raises concerns about its long-term neurotoxic effects. Little is known, however, about DDT toxicity during the early stages of neural development. This study demonstrated that DDT-induced apoptosis of mouse embryonic neuronal cells is a caspase-9-, caspase-3-, and GSK-3 beta-dependent process, which involves p,p'-DDT-specific impairment of classical ERs. It also provided evidence for DDT-isomer-nonspecific alterations of AhR- and GPR30-mediated intracellular signaling, including changes in the levels of the receptor and receptor-regulated mRNAs, and also changes in the protein levels of the receptors. DDT-induced stimulation of AhR-signaling and reduction of GPR30-signaling were verified using selective ligands and specific siRNAs. Co-localization of the receptors was demonstrated with confocal microscopy, and the presence of functional GPR30 was detected by electrophysiology. This study demonstrates that stimulation of AhR-signaling and impairment of GPR30-signaling play important roles in the propagation of DDT-induced apoptosis during the early stages of neural development. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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