通过NCOA4介导的费里替诺法基参与了在精子中触发的铁灭菌
Didi Jia1, Mingming Zhang2, Mengyuan Li2
1Department of health inspection and quarantine, School of Public Health, Anhui Medical University, Hefei, Anhui, China; The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.
Toxicology
|May 20, 2024
概括
暴露于会通过激活NCOA4介导的铁代谢来触发精子中的铁亡,从而导致铁过载和氧化应激. 抑制自或NCOA4可以减轻这些毒性作用.
科学领域:
- 生殖毒理学 生殖毒理学
- 细胞生物学 细胞生物学
- 环境健康 环境健康
背景情况:
- (Cd) 是一种已知可诱导精子的生殖毒素.
- 导致Cd诱导的铁亡的确切机制尚不完全理解.
- 核受体联合激活剂4 (NCOA4) 是铁代谢的关键调节剂,该过程涉及铁通过溶酶体降解,从而释放铁.
研究的目的:
- 阐明自和NCOA4介导的费里丁在精子细胞中诱导的铁死中的作用.
- 调查暴露对细胞铁水平,氧化应激和铁亡标记物的影响.
主要方法:
- GC-1精子细胞暴露于不同度的CdCl2.
- 使用克洛洛昆 (CQ) 抑制了自.
- Ncoa4-siRNA被用来研究NCOA4在Cd触发铁亡中的作用.
主要成果:
- 暴露在Cd中诱导了线粒体损伤,增加了自细胞形成,并增加了细胞内铁,活性氧物种和.
- 在Cd上调调节的费里丁菌标记物 (Ncoa4,Lc3b,Fth1) 和NCOA4/LC3B/FTH1蛋白表达,同时降低p62/SQSTM1.1.
- 用CQ抑制自或敲击Ncoa4改善了Cd诱导的铁过载和铁.
结论:
- 会激活NCOA4介导的费里丁,导致铁的积累和氧化应激,最终导致精子的铁亡.
- 这一途径突出了Cd诱导的生殖毒性的一种新机制.
- 针对NCOA4介导的费里丁菌通路提供了潜在的治疗策略来对抗毒性.
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