糖皮质激素受体抑制nrf2介导的SLC7A11的表达。

IF 8.2 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Free Radical Biology and Medicine Pub Date : 2025-09-04 DOI:10.1016/j.freeradbiomed.2025.09.008

Sarah E. Lacher , Jennifer Krznarich , Daniel C. Levings , Salil Saurav Pathak , Miles Pufall , Yi-Mei Yang , Matthew Slattery

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引用次数: 0

摘要

SLC7A11编码谷氨酸-胱氨酸交换器xCT，它是细胞内抗氧化能力和细胞外谷氨酸水平的关键调节因子。我们已经确定SLC7A11是糖皮质激素受体（GR）的直接靶点。GR激动剂地塞米松抑制SLC7A11在多种细胞类型中的表达，从上皮细胞到星形胶质细胞。地塞米松诱导GR结合SLC7A11位点的多个调控DNA区域，包括两个突出的nrf2靶向抗氧化反应元件（ARE）区域。增强子解剖和染色质免疫沉淀（ChIP）实验支持一种栓系模型，即GR直接与SLC7A11上的ARE-bound NRF2相互作用，并抑制NRF2介导的该基因的激活。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

The Glucocorticoid Receptor Inhibits NRF2-Mediated Expression of SLC7A11

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The Glucocorticoid Receptor Inhibits NRF2-Mediated Expression of SLC7A11

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.

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来源期刊

Free Radical Biology and Medicine 医学-内分泌学与代谢

CiteScore

14.00

自引率

4.10%

发文量

850

审稿时长

22 days

期刊介绍： Free Radical Biology and Medicine is a leading journal in the field of redox biology, which is the study of the role of reactive oxygen species (ROS) and other oxidizing agents in biological systems. The journal serves as a premier forum for publishing innovative and groundbreaking research that explores the redox biology of health and disease, covering a wide range of topics and disciplines. Free Radical Biology and Medicine also commissions Special Issues that highlight recent advances in both basic and clinical research, with a particular emphasis on the mechanisms underlying altered metabolism and redox signaling. These Special Issues aim to provide a focused platform for the latest research in the field, fostering collaboration and knowledge exchange among researchers and clinicians.