Journal article
The Glucocorticoid Receptor Inhibits NRF2-Mediated Expression of SLC7A11
Free radical biology & medicine, Vol.241, pp.53-63
12/16/2025
DOI: 10.1016/j.freeradbiomed.2025.09.008
PMCID: PMC12897988
PMID: 40914322
Abstract
SLC7A11 encodes the glutamate-cystine exchanger xCT, which is a key regulator of intracellular antioxidant capacity and extracellular glutamate levels. We have identified SLC7A11 as a direct target of the glucocorticoid receptor (GR). The GR agonist dexamethasone represses SLC7A11 expression in multiple cell types, from epithelial cells to astrocytes. Dexamethasone induces GR binding to multiple regulatory DNA regions at the SLC7A11 locus, including two prominent NRF2-targeted antioxidant response element (ARE) regions. Enhancer dissection and chromatin immunoprecipitation (ChIP) assays support a tethering model in which GR directly interacts with ARE-bound NRF2 at SLC7A11 and represses NRF2-mediated activation of this gene.
Details
- Title: Subtitle
- The Glucocorticoid Receptor Inhibits NRF2-Mediated Expression of SLC7A11
- Creators
- Sarah E Lacher - University of Minnesota, DuluthJennifer Krznarich - University of Minnesota, DuluthDaniel C Levings - University of Minnesota, DuluthSalil Saurav Pathak - University of Minnesota, DuluthMiles Pufall - University of IowaYi-Mei Yang - University of Minnesota, DuluthMatthew Slattery - University of Minnesota, Duluth
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.241, pp.53-63
- DOI
- 10.1016/j.freeradbiomed.2025.09.008
- PMID
- 40914322
- PMCID
- PMC12897988
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- ELSEVIER SCIENCE INC
- Grant note
- National Institute of General Medical Sciences: R35-GM119553 National Institute of Mental Health: R01-MH129300
The authors wish to acknowledge Madison Brendon and Maria Nunez Hernandez for technical assistance. We would also like to thank the researchers who generated the genome-wide data used in this study. This work was supported by funding from the National Institute of General Medical Sciences (R35-GM119553 to MS) and the National Institute of Mental Health (R01-MH129300 to YMY and MS) .
- Language
- English
- Electronic publication date
- 09/04/2025
- Date published
- 12/16/2025
- Academic Unit
- Biochemistry and Molecular Biology; Chemical and Biochemical Engineering
- Record Identifier
- 9984962545002771
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