缺氧诱导的线粒体ROS和功能在肺动脉内皮细胞中的功能
Harrison Wang1, Teng-Yao Song1, Jorge Reyes-García1,2
1Department of Molecular & Cellular Physiology, Albany Medical College, Albany, NY 12208, USA.
Cells
|November 8, 2024
概括
缺氧会增加肺动脉细胞中的线粒体活性氧物种 (ROS),促进它们的迁移和增殖. 尼古丁增强了扩散,这两种因素都涉及RISP介导的ROS信号,可能导致肺高血压.
科学领域:
- 心血管研究研究心血管研究
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 肺动脉内皮细胞 (PAECs) 通过活性氧物种 (ROS) 参与低毒性肺高血压 (PH).
- 在PAEC中ROS的精确分子机制和功能作用尚不清楚.
研究的目的:
- 为了研究线粒体ROS在PAEC迁移和在缺氧下扩散中的作用.
- 阐明尼古丁对PAECs的影响及其与缺氧ROS信号的相互作用.
主要方法:
- 评估过氧化 (H2O2) 和超氧化 (O2-) 产量,使用Amplex超红色,素和HyPer传感器.
- 采用了伤检测的迁移和Ki67染色/细胞计数的增殖.
- 采用线粒体抑制剂 (rotenone,myxothiazol) 和通过shRNA进行RISP敲击.
主要成果:
- 缺氧显著增加了来自线粒体的PAEC中的H2O2和O2生产.
- 缺氧增强了PAEC的迁移和扩散;单纯的尼古丁增加了扩散,而不是迁移.
- 低氧和尼古丁的同时暴露进一步放大了迁移和扩散.
- RISP knockdown 抑制了缺氧诱导的迁移和扩散,以及尼古丁促进的扩散.
结论:
- 缺氧刺激RISP介导的线粒体ROS产生,推动PAEC的迁移和扩散.
- 尼古丁增加了PAEC的扩散,其作用在很大程度上是由RISP依赖的ROS信号传递中介的.
- 通过RISP介导的线粒体ROS生成,PAECs可能会对PH做出贡献.
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