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Mol Cell Endocrinol. 2014 Jul 5;392(1-2):90-105. doi: 10.1016/j.mce.2014.05.008. Epub 2014 May 21.

Isomer-nonspecific action of dichlorodiphenyltrichloroethane on aryl hydrocarbon receptor and G-protein-coupled receptor 30 intracellular signaling in apoptotic neuronal cells.

Author information

1
Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland. Electronic address: kajta@if-pan.krakow.pl.
2
Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.
3
Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.
4
Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.
5
Department of Genetics and Evolution, Institute of Zoology, Jagiellonian University, 9 Gronostajowa Street, 30-387 Krakow, Poland.
6
Department of Cell Biology and Imaging, Confocal Microscopy Laboratory, Institute of Zoology, Jagiellonian University, 9 Gronostajowa Street, 30-387 Krakow, Poland.
7
Department of Analytical Chemistry, University of Technology, 24 Warszawska Street, 31-155 Krakow, Poland.
8
Laboratory of Genomics and Biotechnology, University of Agriculture, 1B Rędzina Street, 30-274 Krakow, Poland.
9
Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland; Laboratory of Genomics and Biotechnology, University of Agriculture, 1B Rędzina Street, 30-274 Krakow, Poland.

Abstract

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-3β-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.

KEYWORDS:

Bcl-2; Caspases; Estrogen receptors; GSK-3β; Neurotoxicity; Primary neuronal cell cultures

PMID:
24859647
DOI:
10.1016/j.mce.2014.05.008
[Indexed for MEDLINE]

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