一个包含G3BP1-FBXL5-IRP2轴的调节模块决定了由酸酸盐诱导的铁灭菌
Qian Liu1, Fengli Wang2, Yingxian Chen1
1State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Hubei Hongshan Laboratory, Wuhan, Hubei 430070, China.
Journal of hazardous materials
|December 20, 2023
概括
暴露于酸酸盐会通过启动铁亡,一种由铁积累驱动的细胞死亡形式,导致损伤. G3BP1-FBXL5-IRP2通路调节了这一过程,突出了毒性的新机制.
科学领域:
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 污染构成了全球公共卫生威胁.
- 暴露于甲酸盐与损伤有关,但机制尚不清楚.
- 铁,一种依赖于铁的细胞死亡,与脏疾病的发病有关.
研究的目的:
- 为了研究甲引发的损伤的机制.
- 为了探索铁化在酸毒性中的作用.
- 为了确定这个过程中的关键分子参与者.
主要方法:
- 使用HEK293,MEF和HT1080细胞进行体外研究.
- 使用急性损伤的小鼠模型进行体内研究.
- 对G3BP1-FBXL5-IRP2调节轴和铁恒温的分析.
主要成果:
- 暴露于酸酸盐引起了哺乳动物细胞中的铁亡和小鼠中的急性损伤.
- RNA结合蛋白G3BP1对于甲引发的铁灭菌是必不可少的.
- G3BP1通过抑制FBXL5mRNA翻译来稳定IRP2,从而导致铁的积累和脂质过氧化.
结论:
- 亚酸通过G3BP1-FBXL5-IRP2通路诱导铁和损伤.
- 这一途径调节细胞铁平衡和铁细胞死亡.
- 这些发现揭示了诱导毒性的新机制.
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