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Dimethyl sulfoxide stimulates the AhR-Jdp2 axis to control ROS accumulation in mouse embryonic fibroblasts.

Authors :
Wuputra K
Tsai MH
Kato K
Yang YH
Pan JB
Ku CC
Noguchi M
Kishikawa S
Nakade K
Chen HL
Liu CJ
Nakamura Y
Kuo KK
Lin YC
Chan TF
Wu DC
Hou MF
Huang SK
Lin CS
Yokoyama KK
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).)

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