Nrf2 缺乏带来了对红外线和7,12-二甲基的敏感度增加,以及对色素和白血病的易感性
Mingxin Dong1, Ping Yang2, Xinyu Zhang1
1Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
概括
缺乏Nrf2蛋白质的小鼠对辐射和DMBA的敏感性增加,经历严重的免疫抑制和较高的癌症发病率,这是由于抗氧化防御的减少.
科学领域:
- 分子生物学分子生物学
- 毒理学 毒理学 毒理学
- 免疫学 免疫学 免疫学
背景情况:
- 核因素红色素2相关因子2 (Nrf2) 是细胞保护细胞免受氧化和电友应激的关键蛋白质.
- 缺乏Nrf2的小鼠表现出受损的造血复制和增加对骨髓抑制的敏感性.
研究的目的:
- 调查Nrf2缺乏的小鼠对电离辐射 (IR) 和7,12-二甲基 (DMBA) 的不同敏感性.
- 评估Nrf2缺乏对血液生成和免疫系统功能在暴露于IR和DMBA后的影响.
主要方法:
- 缺乏Nrf2的和野生型的小鼠被暴露在4 Gy IR或DMBA中.
- 监测了体重,生存率和血液细胞计数.
- 血液氧化酶-1 (HO1) 和NAD(P) H:氨酸氧化还原酶1 (NQO1) 表达式通过RT-qPCR和西部涂抹分析.
主要成果:
- Nrf2缺乏症加剧了由IR和DMBA引起的血液和免疫系统损伤.
- 缺乏Nrf2的小鼠表现出长时间的骨髓抑制,类似白血病的症状和癌症发病率升高.
- 在Nrf2缺乏的小鼠中,HO1和NQO1水平没有显著增加,这表明受阻的保护通路.
结论:
- 对Nrf2的遗传缺陷会降低抗氧化能力,并损害造血和免疫功能.
- Nrf2-null小鼠表现出对IR和DMBA的高度敏感性,这是由于细胞防御机制受损以及血造干细胞中的DNA修复.
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