内核酶G是一种新的决定心脏缩和线粒体功能的决定因素
Chris McDermott-Roe1, Junmei Ye, Rizwan Ahmed
1Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
Nature
|October 8, 2011
概括
内核酶G (Endog) 功能丧失突变增加左心室质量并损害心脏功能. 这项研究揭示了Endog.
科学领域:
- 心血管遗传学 心血管遗传学
- 线粒体生物学 线粒体生物学
- 系统遗传学 系统遗传学
背景情况:
- 左心室质量 (LVM) 是遗传的,也是死亡风险因素.
- 人们对心脏缩的遗传因素和调节机制知之甚少.
- 全基因组关联研究尚未完全确定LVM的遗传基础.
研究的目的:
- 为了确定导致血压独立的左心室质量的遗传因素.
- 研究内核酶G (Endog) 在心脏缩和功能中的作用.
- 探索Endog在心脏和线粒体生物学中的调节机制.
主要方法:
- 在老鼠模型中应用集成基因组学和系统遗传学.
- 在Endog基因中发现了功能丧失突变.
- 使用心肌细胞培养和Endog删除的小鼠模型.
- 进行了全基因组网络分析,并研究了Endog与线粒体组件的相互作用.
主要成果:
- 在Endog的功能丧失突变与增加的LVM和心脏功能受损有关.
- 在心肌细胞中的内分泌抑制促进了高缩,而没有亲高缩刺激.
- 内分泌物由ERR-α和PGC1α直接调节,并与线粒体DNA相互作用.
- 在小鼠中,内分泌物缺失导致线粒体的枯竭,功能障碍和ROS的产生,导致心肌细胞扩大和肥胖症.
结论:
- 内核酶G在不适应性心脏缩中起着新的作用.
- 线粒体功能障碍和反应性氧物种与心脏病有关.
- 内分泌物是线粒体质量和心脏功能的关键调节者.
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