[在诱导的人类角氨酸细胞恶性转化中NRF2介导的氧化还原应激]
Ting Zhang1, Guangze Yao2, Huiting Chen2
1School of Public Health, Medical College of Soochow University, Suzhou 215123, China.
Wei sheng yan jiu = Journal of hygiene research
|September 23, 2024
概括
化物暴露最初会导致氧化应激,但后来通过NRF2诱导减少应激,从而导致人类角质细胞的恶性转变. 沉默NRF2扭转了这些影响,突出了其在矿诱导的癌症中的作用.
科学领域:
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
- 癌症研究 癌症研究
背景情况:
- 石是一种已知的致癌物质,可以诱导细胞的恶性转变.
- 氧化和还原应激在酸盐诱导的致癌过程中的作用尚未完全理解.
- 核转录因子E2相关因子2 (NRF2) 是细胞回氧稳态的关键调节者.
研究的目的:
- 调查NRF2介导的减少性应激在人类角质细胞的酸盐诱导的恶性转化中的作用.
- 分析多个通道暴露于酸盐的细胞中的氧化还原状态和恶性转化指数.
主要方法:
- 用酸 (NaAsO_2) 培养HaCaT细胞和线粒体谷氨探针,以模拟恶性转变.
- 测量了细胞和线粒体的氧化还原平衡 (GSH/GSSG,NADPH/NADP+).
- 评估了细胞增殖,迁移和软菌殖民地形成. 通过siRNA来评估NRF2的作用,NRF2被静止.
主要成果:
- 早期的化石暴露诱导了氧化应激 (减少了GSH/GSSG),而后期的阶段显示了还原应激 (增加了NADP/NADP+和GSH/GSSG).
- 用酸盐处理的细胞表现出增加的增殖,迁移和殖民地形成,表明恶性转变.
- 抑制NRF2可以逆转这些变化,减少氧化和还原性压力标志物,并抑制恶性表型.
结论:
- 在早期阶段,矿会引起氧化应激,并导致持续的NRF2表达.
- 后来,NRF2的激活会导致减少性压力,促进恶性转变.
- NRF2通过氧化还原调节在酸盐诱导的恶性转变中发挥着关键作用.
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