细胞内网膜压力加剧了动物细胞中微塑料诱导的毒性
Zhanhang Wang1, Shujuan Liu2, Zefang Cheng2
1College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China; Key Laboratory of Livestock Biology Northwest A&F University, Yangling, Shaanxi 712100, China.
聚乙烯微塑料 (PS MPs) 通过引起线粒体功能障碍,氧化应激和内分泌网膜 (ER) 应激而损害山羊乳腺细胞. 抑制ER压力可以减少PSMP诱导的细胞损伤和细胞亡.
科学领域:
- 环境毒理学环境毒理学
- 细胞生物学 细胞生物学
- 哺乳动物细胞研究研究
背景情况:
- 微塑料 (MP) 暴露在食品链中无处不在,对人类和动物的健康构成风险.
- 动物暴露于MPs及其随后的毒性仍未得到充分研究.
- 聚烯微塑料 (PS MP) 是常见的环境污染物.
研究的目的:
- 研究PS MPs对山羊乳腺上皮细胞 (GMEC) 的细胞毒性作用.
- 阐明背后的分子机制PS MP诱导的细胞损伤,包括线粒体和内分泌网膜 (ER) 压力.
- 评估ER应激在PS MP毒性中的作用.
主要方法:
- 将GMEC暴露在不同度的PS MP中.
- 评估细胞活力,形态和器官完整性的评估.
- 线粒体膜潜力和反应性氧物种 (ROS) 检测.
- 转录组分析以确定受影响的细胞通路.
- 研究ER压力标志物 (PERK/eIF2α/CHOP通路) 和细胞内水平.
- 对亡相关途径 (Bax/Bcl-2) 和酶激活的分析.
- 用PERK抑制剂 (ISRIB) 治疗以评估其保护作用.
主要成果:
- PS MPs显著降低了GMEC活力,改变了细胞形态,并破坏了细胞器的完整性.
- 线粒体功能障碍和氧化应激是由PS MPs诱导的.
- 转录组分析显示了与ER恒温相关的途径的显著变化.
- 通过PERK/eIF2α/CHOP通路,PS MPs触发了ER压力,导致细胞内Ca2+过载.
- 通过Bax/Bcl-2通路和酶级联激活诱导了亡.
- 使用ISRIB减弱PSMP诱导的细胞毒性和亡来抑制ER压力.
结论:
- PS MPs对哺乳动物细胞,特别是GMECs具有显著的细胞毒性.
- ER压力,线粒体功能障碍和氧化压力是调解PS MP毒性的关键机制.
- ER压力加剧了PS MP诱导的细胞毒性,突出了其关键作用.
- 这项研究提供了关于MPs在食品中的细胞影响和毒理机制的关键见解.
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