氧化压力介导的四博二甲破坏了HepG细胞中的线粒体功能,并激活了ferroptosis信号,以诱导亡
Xiaotian Huang1, Zuhong Lin1, Denglong Lu1
1Center for Environment and Water Resources, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, PR China; Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety, Changsha, 410083, PR China.
Journal of environmental management
|April 15, 2025
概括
一种阻燃剂Tetrabromobisphenol A (TBBPA) 通过破坏线粒体和增加氧化应激会导致肝细胞死亡. 这项研究揭示了TBBPA通过ROS和铁的积累触发铁,一种特定的细胞死亡途径.
科学领域:
- 环境毒理学环境毒理学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 博二A (TBBPA) 是一种持续性环境污染物,作为阻燃剂使用.
- 众所周知,TBBPA诱导线粒体功能障碍和亡,但机制尚不清楚.
- 氧化应激与TBBPA毒性有关.
研究的目的:
- 研究TBBPA在人类肝癌细胞中的线粒体毒性 (HepG2).
- 阐明TBBPA诱导的特定细胞死亡途径,包括铁亡.
- 描述氧化应激在TBBPA中介细胞毒性的作用.
主要方法:
- 在体外测试中使用暴露于TBBPA的HepG2细胞.
- 测量细胞活力,活性氧物种 (ROS) 水平和线粒体功能 (MMP,OCR,ATP,复杂活动).
- 对自标志物 (LC3B,PINK1,帕金) 和铁灭生物标志物 (Fe2+,MDA,GPX4,SLC7A11,COX-2,Beclin-1) 的分析.
主要成果:
- 10微米的TBBPA诱导了~50%的细胞死亡和细胞活力降低.
- 治疗TBBPA显著增加了细胞内ROS水平.
- 线粒体功能障碍被减少的MMP,OCR,ATP和改变的呼吸链复杂活动证实.
- 暴露于TBBPA导致铁亡,由Fe2+和MDA的增加和关键铁亡蛋白的改变表达证明.
结论:
- 在HepG2细胞中,TBBPA诱导显著的细胞毒性.
- TBBPA破坏了线粒体的功能,并促进了氧化应激.
- 铁亡是TBBPA诱导的肝细胞死亡的关键机制.
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