通过激活NRF2/HO-1铁亡路来调节Cd诱导的生殖损伤的反应因子ATF3
Sisi Li1, Sheng Ma1, Lirui Wang1
1School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China; Shanghai Key Laboratory for Veterinary and Biotechnology, Shanghai 200240, China.
Ecotoxicology and environmental safety
|October 2, 2024
概括
暴露于会通过ATF3介导的NRF2/HO-1通路诱导男性生殖细胞中的铁亡,从而导致丸损伤. 了解这种机制为生殖毒性提供了新的治疗点.
科学领域:
- 生殖毒理学 生殖毒理学
- 细胞机制 细胞机制
- 环境健康 环境健康
背景情况:
- (Cd) 是一种已知诱导铁亡的生殖毒素.
- 精确的Cd诱导的生殖细胞铁亡的分子途径尚未完全阐明.
- 了解这些机制对于解决男性生殖健康问题至关重要.
研究的目的:
- 系统地研究Cd诱导的生殖细胞ferroptosis的分子机制.
- 确定涉及该过程的关键转录因子和蛋白质.
- 探索潜在的治疗干预措施.
主要方法:
- 对雄性小鼠口服化 (CdCl2) 并对TM3和TM4细胞系进行治疗.
- 评估铁过载,氧化应激和线粒体形态.
- RNA测序以识别差异性基因表达.
- 针对ferroptosis和HO-1活动的干预研究.
- 对ATF3和NRF2通路激活的分析.
主要成果:
- 暴露于Cd会导致铁过载,氧化应激和线粒体损伤,这表明丸中的铁亡.
- 在Cd暴露的生殖细胞中观察到Atf3和Hmox1 (HO-1) 的显著上调.
- 干预铁或HO-1缓解的Cd诱导的细胞死亡.
- ATF3过度表达激活了Keap1-Nrf2通路,增加了NRF2和HO-1表达,并促进了铁亡.
- 在ATF3沉默下,逆转了NRF2和HO-1表达水平.
结论:
- 通过ATF3介导的NRF2/HO-1信号通路的激活来诱导生殖细胞铁亡.
- 这一途径有助于丸损伤和生殖毒性.
- 准ATF3-NRF2/HO-1轴为治疗Cd诱导的丸损伤提供了一个潜在的策略.
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