通过中断线粒体平衡,SERCA2功能障碍会引发高血压,并引发氧化应激
Yaping Wang1, Min Wang1, Hang Su2
1Innovative Drug Research Centre, Chongqing University, Chongqing, 401331, China.
Free radical biology & medicine
|January 1, 2024
概括
功能障碍的 Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) 由于囊素674的氧化,通过诱导氧化应激会增加血压. 激活SERCA2或抑制氧化应激可以缓解高血压.
科学领域:
- 心血管生理学心血管生理学
- 脏生理学 脏生理学
- 细胞生物学 细胞生物学
背景情况:
- 体/内体网膜Ca2+ ATPase 2 (SERCA2) 对于Ca2+稳态至关重要.
- 在SERCA2中氨酸674 (C674) 的氧化与高血压有关.
- 在C674处的SERCA2功能障碍可以诱导细胞内网膜应激 (ERS) 并提高血压.
研究的目的:
- 为了调查SERCA2功能障碍是否通过破坏线粒体平衡和增加氧化应激来加剧高血压.
- 探索SERCA2激活和氧化应激抑制在高血压小鼠模型中的治疗潜力.
主要方法:
- 使用异质合体SERCA2 C674S基因突变敲进 (SKI) 鼠标.
- 对线粒体功能,ATP,活性氧物种 (ROS) 和ERS标志物的近管 (RPT) 细胞进行了分析.
- 在SKI小鼠中使用SERCA2激动剂 (CDN1163, [6]-醇) 和氧化还原调节剂 (Tempol).
主要成果:
- 在RPT细胞中,SERCA2 C674S突变降低了线粒体Ca2+和增加了ROS.
- 在SKI RPT细胞中,波治疗减少了氧化应激,ERS标记物,并改善了Na+/K+-ATPase活性.
- 在SKI小鼠中的药理干预增加了尿量,降低了血压.
结论:
- 无法逆转的C674氧化SERCA2通过增加的氧化应激导致高血压.
- 激活SERCA2或抑制氧化应激表明,在管理与SERCA2功能障碍相关的高血压方面具有前途.
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