Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8477190 | Molecular and Cellular Endocrinology | 2014 | 16 Pages |
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
Ac-DEVD-pNaPHTPPGSK-3βERαERβdichlorodiphenyltrichloroethanesEPSCBcl-2ARNTGPR30HprtMPPZ-LEHD-FMKqPCRG15AHRG-protein-coupled receptor 30DMSOaryl hydrocarbon receptor nuclear translocatorICI 182,780ELISAEnzyme-linked immunosorbent assayspontaneous excitatory postsynaptic currentDIVDDTDimethyl sulfoxideday in vitroreverse transcriptionNeurotoxicitylactate dehydrogenaseLDHquantitative polymerase chain reactionWestern blottingCaspasesGlycogen synthase kinase 3βaryl hydrocarbon receptorEstrogen receptorEstrogen receptor alphaEstrogen receptor betaestrogen receptors
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Authors
M. Kajta, E. Litwa, J. Rzemieniec, A. Wnuk, W. Lason, A. Zelek-Molik, I. Nalepa, M. Grzegorzewska-Hiczwa, K. Tokarski, A. Golas, E. Guzik, A. Grochowalski, K.A. Szychowski, A.K. Wojtowicz,