通过Pgam5介导的PHB2脱酸化,通过抑制线粒体和线粒体未折叠蛋白质反应,有助于因内毒素引起的心肌功能障碍
Chen Cai1,2, Ziying Li1,2, Zemao Zheng3
1Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
International journal of biological sciences
|October 2, 2023
概括
禁忌素2 (PHB2) 通过激活线粒体和线粒体未折叠蛋白质反应 (UPRmt) 来预防内毒素引起的心脏功能障碍. Pgam5去酸化PHB2,影响其线粒体局部化和保护功能.
科学领域:
- 心血管生物学 心血管生物学
- 线粒体生物学 线粒体生物学
- 细胞应激反应的应激反应
背景情况:
- 内毒素导致心脏中的线粒体功能障碍.
- 在内毒素引起的心脏功能障碍中,禁忌素2 (PHB2) 和糖酸突变酶5 (Pgam5) 的作用尚不清楚.
- 线粒体和线粒体展开蛋白反应 (UPRmt) 是线粒体完整性的关键.
研究的目的:
- 研究Pgam5和PHB2在心肌细胞内因内毒素引起的线粒体功能障碍中的作用.
- 检查米托法基和UPRmt在这个过程中的参与.
主要方法:
- 使用PHB2转基因小鼠和HL-1心肌细胞.
- 使用LPS诱导类似于内毒素的状况.
- 进行了分子分析,包括基因沉默和突变变异.
- 评估心肌细胞活力和线粒体功能.
主要成果:
- 转基因PHB2小鼠表现出对内毒素引起的心肌抑制和线粒体损伤的抗性.
- 过度表达PHB2激活了线粒和UPRmt,保持了线粒体代谢和活力.
- Pgam5去酸化PHB2,导致其细胞体转位.
- 沉默Pgam5或PHB2突变性转染保存了线粒体PHB2并激活了保护性通路.
结论:
- 在内毒性期间,PHB2通过线粒和UPRmt保护心肌细胞.
- Pgam5负面调节PHB2的线粒体定位和保护功能.
- Pgam5/PHB2信号通路和线粒/UPRmt是内毒性相关心脏功能障碍的潜在治疗点.
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