Triclocarban Disrupts the Epigenetic Status of Neuronal Cells and Induces AHR/CAR-Mediated Apoptosis
| العنوان: | Triclocarban Disrupts the Epigenetic Status of Neuronal Cells and Induces AHR/CAR-Mediated Apoptosis |
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| المؤلفون: | Anna Wójtowicz, I. Nehring, Joanna Rzemieniec, E. Chwastek, Małgorzata Kajta, M. Mackowiak, Agnieszka Wnuk, M. Staniszewska, W. Lason |
| المصدر: | Molecular Neurobiology |
| بيانات النشر: | Springer US, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Small interfering RNA, Neuroscience (miscellaneous), Receptors, Cytoplasmic and Nuclear, Apoptosis, Biology, Hippocampus, Article, Histone Deacetylases, Epigenesis, Genetic, 03 medical and health sciences, Cellular and Molecular Neuroscience, Mice, 0302 clinical medicine, Primary neurons, Constitutive androstane receptor, medicine, Animals, Sirtuins, Epigenetics, DNA (Cytosine-5-)-Methyltransferases, RNA, Messenger, RNA, Small Interfering, Receptor, Cells, Cultured, Constitutive Androstane Receptor, bcl-2-Associated X Protein, Membrane Potential, Mitochondrial, Neurons, DNA methylation, L-Lactate Dehydrogenase, Staining and Labeling, Caspase 3, Triclocarban, Neurotoxicity, Sumoylation, medicine.disease, Aryl hydrocarbon receptor, Cell biology, 030104 developmental biology, Neurology, Receptors, Aryl Hydrocarbon, biology.protein, Reactive Oxygen Species, 030217 neurology & neurosurgery, Carbanilides, DNA hypomethylation |
| الوصف: | Triclocarban is a phenyl ether that has recently been classified as a contaminant of emerging concern. Evidence shows that triclocarban is present in human tissues, but little is known about the impact of triclocarban on the nervous system, particularly at early developmental stages. This study demonstrated that triclocarban that was used at environmentally relevant concentrations induced apoptosis in mouse embryonic neurons, inhibited sumoylation, and changed the epigenetic status, as evidenced by impaired activities of HDAC, sirtuins, and DNMT, global DNA hypomethylation, and alterations of methylation levels of bax, bcl2, Ahr, and Car genes. The use of selective antagonists and specific siRNAs, which was followed by the co-localization of aryl hydrocarbon receptor (AHR) and constitutive androstane receptor (CAR) in mouse neurons, points to the involvement of AHR and CAR in triclocarban-induced neurotoxicity. A 24-h treatment with triclocarban enhanced protein levels of the receptors which was paralleled by Car hypomethylation and Ahr hypermethylation. Car hypomethylation is in line with global DNA hypomethylation and explains the increased mRNA and protein levels of CAR in response to triclocarban. Ahr hypermethylation could reflect reduced Ahr mRNA expression and corresponds to lowered protein levels after 3- and 6-h exposures to triclocarban that is likely related to proteasomal degradation of activated AHR. We hypothesize that the triclocarban-induced apoptosis in mouse neurons and the disruption of epigenetic status involve both AHR- and CAR-mediated effects, which may substantiate a fetal basis of the adult onset of neurological diseases; however, the expression of the receptors is regulated in different ways. |
| اللغة: | English |
| تدمد: | 1559-1182 0893-7648 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::20d718028dc9c8a620feafe47b784192Test http://europepmc.org/articles/PMC6476872Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....20d718028dc9c8a620feafe47b784192 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15591182 08937648 |
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