聚甲基胺酸通过气体反应性物种调节的支气管上皮质细胞中的线粒体功能障碍诱导热
Jun Young Park1, Ji-Hee Kim2, Chan Ho Park3
1Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
Toxicology
|May 10, 2024
概括
聚乙烯瓜尼丁 (PHMG) 通过诱导细胞死亡途径 - - 热亡 - - 引发肺损伤. 这通过线粒体的活性氧物种 (ROS) 和支气管细胞的功能障碍发生.
科学领域:
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
- 肺部医学 肺部医学
背景情况:
- 热致死是一种被编程的细胞死亡机制,涉及气体皮膜 (GSDM) 孔和炎症性细胞因子释放.
- 肺部疾病越来越多地与热症有关.
- 由于聚甲基瓜尼丁 (PHMG) 引起的肺毒性,背后的机制尚不清楚.
研究的目的:
- 为了研究火灭菌在PHMG诱导的肺毒性中的作用.
- 阐明PHMG对支气管上皮细胞的影响背后的细胞机制.
主要方法:
- 对BEAS-2B支气管上皮细胞暴露于PHMG酸盐 (PHMG-p).
- 评估细胞活力,形态,活性氧物种 (ROS) 水平和与热死相关的蛋白质表达.
- 评估线粒体功能和蛋白质转位.
主要成果:
- 暴露于PHMG-p减少了细胞活力和改变了细胞形态.
- PHMG-p诱导了线粒体ROS (mtROS) 的显著积累.
- PHMG-p激活了由mtROS和线粒体功能障碍驱动的apoptosis和GSDMD/GSDME介导的pyroptosis,包括Bax和分裂的GSDM转位.
结论:
- 通过在支气管上皮细胞中激活 pyroptosis,PHMG-p 诱导肺毒性.
- 线粒体氧化应激和随后的功能障碍是PHMG诱导热的关键媒介.
- 这项研究澄清了PHMG肺毒性的分子机制.
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