NSUN2依赖ALYREF来调节Nrf2介导的氧化应激,并缓解Dox诱导的肝损伤
Yingying Huang1, Xiao Li1, Lin Wei1
1Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
Biology direct
|April 29, 2024
概括
核因子红色素2相关因子2 (Nrf2) 通过增加抗氧化应激来防止多克索鲁比 (Dox) 诱导的肝损伤. NSUN2调节Nrf2mRNA甲基化,影响肝细胞损伤.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 德克索鲁比 (Dox) 化疗可以导致严重的肝损伤,限制其使用.
- 在Dox诱导的肝毒性中NSUN2的作用尚不清楚.
研究的目的:
- 为了调查NSUN2在Dox引起的肝损伤中的参与.
- 阐明NSUN2在这个过程中的作用背后的分子机制.
主要方法:
- 建立了Dox诱导的肝损伤的体内和体外模型.
- 通过Western blot评估了NSUN2和氧化应激标记物的蛋白质水平 (Nrf2,HO-1,NQO1).
- 利用RNA免疫沉 (RIP) 和RNA光探针来评估NSUN2-Nrf2mRNA相互作用和调节.
主要成果:
- 德克索鲁比辛治疗降低了NSUN2的调节,并导致肝损伤,由高ALT/AST水平证明.
- NSUN2的敲除会使Dox诱导的肝损伤恶化,而NSUN2的过度表达则会对肝损伤进行保护.
- NSUN2直接与Nrf2mRNA结合,提高Nrf2蛋白水平,并激活Nrf2 5'UTR区域,这一过程依赖于ALYREF.
结论:
- NSUN2通过甲基化Nrf2mRNA (m5C) 来保护Dox诱导的肝损伤,从而增强抗氧化应激反应.
- 在Nrf2上NSUN2的调节功能通过其与ALYREF的相互作用来调节.
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