通过AhR/ROS介导的内质网膜应激会导致PFOSA诱导的心脏缺陷
Kang Wang1, Huixian Chen1, Pinyi Chen1
1The First Affiliated Hospital, MOE Education Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, China.
Toxicology
|December 3, 2025
概括
暴露在 perfluorooctane sulfonamide (PFOSA) 中会导致斑马鱼的心脏缺陷,因为它通过阿里碳水化合物受体 (AhR) 和活性氧物种 (ROS) 途径诱导细胞内网膜应激 (ERS).
科学领域:
- 环境毒理学环境毒理学
- 发展生物学 发展生物学
- 分子毒理学 分子毒理学
背景情况:
- perfluorooctane sulfonamide (PFOSA) 是一种环境污染物,也是PFOS的前体.
- 酸受体 (AhR) 与PFOSA诱导的心脏缺陷有关,但机制尚不清楚.
- 在斑马鱼中,PFOSA暴露后,内质网膜压力 (ERS) 基因被上调.
研究的目的:
- 调查ERS在PFOSA诱导的心脏发育毒性的作用.
- 阐明AhR调解PFOSA毒性的机制.
- 为了检查展开蛋白质反应 (UPR) 和线粒体功能障碍的PERK分支的参与.
主要方法:
- 斑马鱼幼虫和老鼠心肌细胞暴露于PFOSA.
- 对ERS标记物的测量 (Grp78,Chop).
- 抑制AhR和活性氧物种 (ROS).
- 评估线粒体水平和PGC-1α表达.
主要成果:
- PFOSA暴露增加了ERS标志物 (Grp78,Chop) 以剂量依赖的方式.
- 抑制AhR和ROS减弱了PFOSA诱导的ERS和PERK激活.
- 由PFOSA诱导的ERS导致线粒体过载和PGC-1α下调.
- 在斑马鱼胚胎和老鼠心肌细胞中观察到亡和心脏缺陷.
结论:
- 通过依赖于AhR/ROS的ERS通路,PFOSA诱导心脏发育毒性.
- ERS激活了PERK分支,导致线粒体损伤和亡.
- 在PFOSA的心脏毒性方面,ERS起着至关重要的作用.
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