Triclocarban Disrupts the Epigenetic Status of Neuronal Cells and Induces AHR/CAR-Mediated Apoptosis.

摘要: Triclocarban is a phenyl ether that has recently been classified as contaminant of emerging concern. Evidence shows triclocarban present in human tissues, but little known about the impact on nervous system, particularly at early developmental stages. This study demonstrated was used environmentally relevant concentrations induced apoptosis mouse embryonic neurons, inhibited sumoylation, and changed epigenetic status, evidenced by impaired activities HDAC, sirtuins, DNMT, global DNA hypomethylation, alterations methylation levels bax, bcl2, Ahr, Car genes. The use selective antagonists specific siRNAs, which followed co-localization aryl hydrocarbon receptor (AHR) constitutive androstane (CAR) points to involvement AHR CAR triclocarban-induced neurotoxicity. A 24-h treatment with enhanced protein receptors paralleled hypomethylation Ahr hypermethylation. line explains increased mRNA response triclocarban. hypermethylation could reflect reduced expression corresponds lowered after 3- 6-h exposures likely related proteasomal degradation activated AHR. We hypothesize neurons disruption status involve both AHR- CAR-mediated effects, may substantiate fetal basis adult onset neurological diseases; however, regulated different ways.