期刊
NEUROTOXICITY RESEARCH
卷 29, 期 1, 页码 155-172出版社
SPRINGER
DOI: 10.1007/s12640-015-9572-6
关键词
Neurotoxicity; Retinoid X receptor; RXR; DDE; DDT; Primary neuronal cell cultures
资金
- Operating Program of Innovative Economy [POIG.01.01.02-12-004/09]
- Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland
- KNOW - Ministry of Science and Higher Education, Poland
- Jagiellonian University within the SET project
- European Union
Dichlorodiphenyldichloroethylene (DDE) is a primary environmental and metabolic degradation product of the pesticide dichlorodiphenyltrichloroethane (DDT). It is one of the most toxic compounds belonging to organochlorines. DDE has never been commercially produced; however, the parent pesticide DDT is still used in some developing countries for disease-vector control of malaria. DDT and DDE remain in the environment because these chemicals are resistant to degradation and bioaccumulate in the food chain. Little is known, however, about DDE toxicity during the early stages of neural development. The results of the present study demonstrate that DDE induced a caspase-3-dependent apoptosis and caused the global DNA hypomethylation in mouse embryonic neuronal cells. This study also provided evidence for DDE-isomer-non-specific alterations of retinoid X receptor alpha (RXR alpha)- and retinoid X receptor beta (RXR beta)-mediated intracellular signaling, including changes in the levels of the receptor mRNAs and changes in the protein levels of the receptors. DDE-induced stimulation of RXR alpha and RXR beta was verified using selective antagonist and specific siRNAs. Co-localization of RXR alpha and RXR beta was demonstrated using confocal microscopy. The apoptotic action of DDE was supported at the cellular level through Hoechst 33342 and calcein AM staining experiments. In conclusion, the results of the present study demonstrated that the stimulation of RXR alpha- and RXR beta-mediated intracellular signaling plays an important role in the propagation of DDE-induced apoptosis during early stages of neural development.
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