通过CTH/H2S/Drp1信号通路诱导肝细胞亡
Jie Zhou1, Xin Zheng1, Chen Xi2
1School of Medicine, Yichun University,576 XueFu Road, Yuanzhou District, Yichun 336000, PR China.
The Science of the total environment
|August 8, 2024
概括
六价 (Cr(VI)) 通过破坏CTH/H2S/Drp1通路导致肝损伤,导致氧化应激和亡. 提高硫化 (H2S) 含量可以防止CrVI引起的肝损伤.
科学领域:
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 六价 (Cr(VI)) 是一种有毒的重金属,与职业性肝损伤有关.
- 精确的Cr (VI) 诱导的肝毒性机制尚未完全理解.
- 线粒体功能障碍和亡与重金属毒性有关.
研究的目的:
- 调查氨酸γ-酶 (CTH) /硫化 (H2S) /动氨酸相关蛋白1 (Drp1) 途径在CrVI诱导的肝损伤中的作用.
- 阐明Cr(VI) 毒性的分子机制,重点关注氧化应激和线粒体通路.
- 为了确定Cr (VI) 诱导的肝毒性潜在的治疗点.
主要方法:
- 利用AML12细胞和小鼠肝脏模型来研究Cr (VI) 效应.
- 评估了亡,反应性氧物种 (ROS) 水平和线粒体功能.
- 测量了CTH和Drp1的S-硫化和Drp1在Serine 616.6的酸化.
- 研究了Drp1和电压依赖性离子通道1 (VDAC1) 之间的相互作用.
主要成果:
- 暴露于Cr(VI) 诱导了亡,增加了ROS,并损害了线粒体功能.
- Cr (VI) 降低了H2S水平,CTH和Drp1的S硫化,同时增加了Drp1的酸化.
- Cr(VI) 促进了 Drp1 的线粒体转位和与 VDAC1 的相互作用,导致了亡.
- 升高的H2S水平逆转了Cr(VI) 诱导的Drp1变化,并保护了肝脏免受损伤.
结论:
- 通过抑制CTH/H2S/Drp1通路,Cr(VI) 诱导线粒体亡和肝损伤.
- 通过Drp1酸化和VDAC1相互作用破坏线粒体的完整性.
- 调节CTH/H2S通路或Drp1 S-硫化为Cr(VI) 肝毒性提供了一个潜在的治疗策略.
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