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在氧化应激下,DEXH-Box酶9参与了De Novo Nrf2蛋白转化
Wujing Dai1, Hongting Diao1, Han Qu1
1Department of Pharmacy Practice and Science, University of Arizona College of Pharmacy, 1295 N. Martin Ave, Tucson, AZ 85721.
Molecular & cellular proteomics : MCP
|April 25, 2025
概括
在氧化应激过程中,DExH-盒酶-9 (DHX9) 与Nrf2mRNA结合,促进Nrf2蛋白合成. 这一发现揭示了细胞防御氧化损伤的新机制.
科学领域:
- 分子生物学分子生物学
- 细胞应激反应的应激反应
- 基因规则 基因规则
背景情况:
- 核因子红色素2相关因子2 (Nrf2) 是一个转录因子,对细胞防御氧化应激至关重要.
- Nrf2控制抗氧化和排毒基因的表达.
- 在氧化应激条件下,Nrf2蛋白水平通过de novo蛋白转化而增加.
研究的目的:
- 为了确定负责结合 Nrf2 mRNA 5'UTR. 的蛋白质.
- 在氧化应激下阐明Nrf2 de novo转化机制.
- 研究DExH-box化酶-9 (DHX9) 在调节Nrf2蛋白合成中的作用.
主要方法:
- RNA免疫沉降试验检测到DHX9与Nrf2 mRNA结合.
- 通过siRNA介导的DHX9.9的淘汰和药理抑制.
- 西方涂抹测量Nrf2蛋白质水平.
- 核糖体分离和分析与核糖体的蛋白质关联.
- 过氧化 (H2O2) 处理以诱导氧化应激.
主要成果:
- DHX9与Nrf2mRNA的5'UTR结合,在H2O2处理下结合增加.
- 抑制DHX9阻断H2O2诱导的Nrf2mRNA招募到核糖体和Nrf2蛋白升高.
- 在氧化应激过程中,DHX9转移到细胞质中并与核糖体结合.
- DHX9与eIF3η的相互作用依赖于RNA,并因氧化应激而增强.
结论:
- 在氧化应激下,DHX9是Nrf2 de novo翻译的关键调节者.
- DHX9通过与其5'UTR结合来促进Nrf2的翻译启动,从而有可能去除抑制性RNA元素.
- 这种机制为细胞对氧化应激的适应性反应提供了新的见解.
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