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COX5A通过抑制氧化应激,线粒体功能障碍和心肌细胞亡来减轻多克索鲁比诱导的心脏毒性
Peipei Zhang1, Hao Lu1, Yuan Wu1
1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Shanghai 200032, China.
International journal of molecular sciences
|June 28, 2023
概括
细胞染色体c氧化酶子单元5A (COX5A) 保护免受多克索鲁比诱导的心肌病变. 抑制COX5A通过激活PI3K/Akt信号来改善心脏功能和线粒体健康.
科学领域:
- 心脏病学 心脏病学
- 线粒体生物学 线粒体生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 多克索鲁比 (DOX) 化疗可以诱导心脏毒性,通过线粒体功能障碍导致心力衰竭.
- 细胞染色体c氧化酶子单元5A (COX5A) 对于线粒体能量代谢至关重要.
- 在DOX诱导心肌病 (DIC) 中COX5A的作用在很大程度上仍未被探索.
研究的目的:
- 研究COX5A在DOX诱导心肌病中的保护作用.
- 阐明COX5A在DIC中的作用的潜在分子机制.
主要方法:
- 在C57BL/6J小鼠和H9c2心肌细胞中进行DOX治疗.
- 腺相关病毒 (AAV9) 和用于COX5A上调的lentivirus系统.
- 采用了心声学,组织学,传输电子显微镜,免疫光学和西式涂抹.
主要成果:
- 心脏COX5A表达在人类扩张性心肌病 (DCM) 和DOX治疗小鼠/细胞中显著下降.
- 过度表达COX5A改善了DOX诱导的心脏功能障碍,线粒体损伤,氧化应激和亡.
- COX5A通过PI3K/Akt信号传递对Akt (Thr308和Ser473) 的酸化进行上调,调解其保护作用.
结论:
- COX5A对多克索鲁比诱导的心脏毒性起着关键的保护作用.
- COX5A可以缓解线粒体功能障碍,氧化应激和心肌细胞亡.
- PI3K/Akt通路对于COX5A介导的心脏保护至关重要,它将COX5A确定为DIC的潜在治疗标.
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