费罗斯塔丁-1通过重编程线粒体功能,在大动脉内皮细胞中逆转慢性间歇性缺氧诱导的铁亡
Jia Chen1,2,3,4, Xiaoyu Deng1,2,3,4, Ting Lin1,2,3,4
1Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
Nature and science of sleep
|April 29, 2024
概括
慢性间歇性缺氧会诱导大鼠动脉内皮细胞中的铁亡. 铁素-1治疗通过改善线粒体功能和重编程新陈代谢来逆转这种损伤.
科学领域:
- 心血管生物学 心血管生物学
- 细胞生理学 细胞生理学
- 生物化学 生物化学
背景情况:
- 慢性间歇性缺氧 (CIH) 是动脉内皮损伤和心血管疾病的重要贡献者.
- 在CIH诱导的内皮损伤背后的精确机制仍然不完全理解.
- 铁死是一种受调节的细胞死亡形式,与内皮功能障碍有关,但需要进一步的机械研究.
研究的目的:
- 阐明铁素-1 (Fer-1) 在减轻大鼠动脉内皮细胞 (ROAEC) 中CIH诱导的铁亡的作用和潜在机制.
- 调查CIH和Fer-1治疗对细胞活力,氧化应激标志物和关键铁亡相关蛋白质 (SLC7A11,GPX4) 的影响.
- 评估CIH和Fer-1对线粒体结构,功能和中央碳代谢的影响.
主要方法:
- 鼠类动脉内皮细胞 (ROAEC) 接受了控制条件,CIH或CIH与fer-1治疗.
- 细胞活力 (CCK8),细胞亡率,反应性氧物种 (ROS),Fe2+,脂质ROS和甲 (MDA) 都被量化.
- 分析了NAD+/NADH比率,SLC7A11和GPX4表达 (mRNA和蛋白质),线粒体形态 (TEM),线粒体膜潜力 (MMP) 和中央碳代谢.
主要成果:
- 暴露于CIH显著降低了ROAEC活力,同时增加了亡,ROS,Fe2+,MDA和脂质ROS水平.
- CIH导致NAD+/NADH比率下降,GPX4和SLC7A11的表达减少,伴随着线粒体损伤和减少MMP.
- 铁-1治疗有效地逆转了这些有害影响,恢复了细胞活力,减少了氧化应激,使NAD+/NADH比率正常化,提高了GPX4和SLC7A11的调节,并改善了线粒体功能障碍和代谢变化.
结论:
- CIH在老鼠动脉内皮细胞中诱导铁,其特征是氧化应激和线粒体功能障碍.
- 费罗斯塔丁-1通过恢复线粒体功能和重编程中央碳代谢,有效地保护CIH诱导的内皮铁.
- 这些发现强调了铁化作为CIH相关的内皮损伤的关键机制,并建议Fer-1作为潜在的治疗剂.
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