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Dimethyl sulfoxide stimulates the AhR-Jdp2 axis to control ROS accumulation in mouse embryonic fibroblasts.
- Source :
-
Cell biology and toxicology [Cell Biol Toxicol] 2022 Apr; Vol. 38 (2), pp. 203-222. Date of Electronic Publication: 2021 Mar 15. - Publication Year :
- 2022
-
Abstract
- The aryl hydrocarbon receptor (AhR) is a ligand-binding protein that responds to environmental aromatic hydrocarbons and stimulates the transcription of downstream phase I enzyme-related genes by binding the cis element of dioxin-responsive elements (DREs)/xenobiotic-responsive elements. Dimethyl sulfoxide (DMSO) is a well-known organic solvent that is often used to dissolve phase I reagents in toxicology and oxidative stress research experiments. In the current study, we discovered that 0.1% DMSO significantly induced the activation of the AhR promoter via DREs and produced reactive oxygen species, which induced apoptosis in mouse embryonic fibroblasts (MEFs). Moreover, Jun dimerization protein 2 (Jdp2) was found to be required for activation of the AhR promoter in response to DMSO. Coimmunoprecipitation and chromatin immunoprecipitation studies demonstrated that the phase I-dependent transcription factors, AhR and the AhR nuclear translocator, and phase II-dependent transcription factors such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) integrated into DRE sites together with Jdp2 to form an activation complex to increase AhR promoter activity in response to DMSO in MEFs. Our findings provide evidence for the functional role of Jdp2 in controlling the AhR gene via Nrf2 and provide insights into how Jdp2 contributes to the regulation of ROS production and the cell spreading and apoptosis produced by the ligand DMSO in MEFs.<br /> (© 2021. The Author(s).)
- Subjects :
- Animals
Dimethyl Sulfoxide pharmacology
Fibroblasts metabolism
Ligands
Mice
NF-E2-Related Factor 2 genetics
NF-E2-Related Factor 2 metabolism
Reactive Oxygen Species metabolism
Polychlorinated Dibenzodioxins pharmacology
Receptors, Aryl Hydrocarbon genetics
Receptors, Aryl Hydrocarbon metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-6822
- Volume :
- 38
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell biology and toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 33723743
- Full Text :
- https://doi.org/10.1007/s10565-021-09592-2