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线粒体的活性氧物种改变了细胞外囊泡的分泌率
Mikkel Ø Nørgård1, Philip M Lund2, Nazmie Kalisi3
1Department of Molecular Medicine, Cardiovascular and Renal Research University of Southern Denmark Odense Denmark.
缺氧刺激了细胞外囊泡 (EV) 的分泌. 线粒体电子运输链 (ETC) 刺激增加了EV分泌,由活性氧物种 (ROS) 驱动,而不是HIF-1信号.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 线粒体生物学 线粒体生物学
背景情况:
- 细胞外囊泡 (EV) 分泌受细胞应激的影响,包括缺氧.
- 反应性氧物种 (ROS) 和缺氧诱导因子 (HIF) -1 信号与EV产生有关,但它们的具体作用尚不清楚.
研究的目的:
- 研究线粒体电子运输链 (ETC) 活动和HIF-1信号对缺氧诱导的EV分泌的独特贡献.
- 确定ROS在调节EV分泌率中的作用.
主要方法:
- 利用一个EV记者细胞系 (CD9truc-EGFP) 来量化EV分泌率.
- 使用的HIF-1α稳定剂 (roxadustat),ETC刺激剂 (二乙酸 - DCA),ETC抑制剂 (rotenone,抗菌素A),抗氧化剂 (TEMPO) 和代谢途径抑制剂 (pitavastatin,4-nitrobenzoate).
- 在正常和缺氧条件下操纵线粒体ETC活性和ROS产生.
主要成果:
- HIF-1α稳定没有影响EV分泌率.
- 与DCA一起的ETC刺激显著增加了EV分泌,这种效果被罗诺 (复合I抑制剂) 和TEMPO (抗氧化剂) 阻止.
- 抑制ETC复合物III模仿缺氧和增加ROS依赖的EV分泌,进一步得到了代谢途径干预的支持.
结论:
- 线粒体ETC活动,特别是ROS产生,是模拟缺氧条件下增加EV分泌的关键驱动因素.
- 针对ETC的低氧模拟剂可以调节EV分泌,突出显示ROS是EV释放的强有力的刺激.
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