持续高的NRF2表达抑制了化转化的人类角质细胞中的细胞亡
Qianlei Yang1, Ting Zhang1, Jian Liu2
1Department of Toxicology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, 215123, Jiangsu, China.
概括
暴露于酸盐会激活核因子-erythroid-2 p45相关因子2 (NRF2),减少细胞亡并促进皮肤癌. 沉默NRF2扭转了这些影响,突出了NRF2的作用.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 毒理学 毒理学 毒理学
背景情况:
- 核因子 - - 血红素-2 p45相关因子2 (NRF2) 在酸盐诱导的瘤发生中被激活.
- NRF2在诱导的皮肤致癌细胞亡中的机制尚不清楚.
研究的目的:
- 调查NRF2在酸盐诱导的HaCaT细胞恶性转变期间在亡中的作用.
- 探索亡和相关蛋白质的动态变化.
主要方法:
- 在多个通道中培养了具有1.0微米NaAsO2的不朽的人类角质细胞 (HaCaT).
- 评估的亡速率和蛋白质表达 (caspase-3,CHOP,ATF4,ATF6,Bax,BCL-2,Mcl-1,NRF2) 的情况.
- 沉默NRF2在化转化HaCaT (T-HaCaT) 细胞中,以评估细胞亡和细胞功能.
主要成果:
- 在后来的段落中,亡率和裂开的caspase-3/caspase-3比率下降.
- NRF2,Bcl-2和Mcl-1的水平增加,而CHOP,ATF4,ATF6和Bax的水平下降.
- 沉默NRF2增加了亡,减少了殖民地形成/迁移,并上调了亲亡蛋白.
结论:
- 酸盐在后期阶段激活NRF2,抑制ER和线粒体亡途径.
- NRF2通过减少亡来促进酸盐诱导的HaCaT细胞恶性转变.
- 向NRF2可能为素诱导的皮肤致癌提供治疗策略.
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