在心力衰竭进展过程中蛋白酸酶1相互作用的重新排列
David Y Chiang1,2,3, Katherina M Alsina2,4, Eleonora Corradini3,5
1Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.Y.C.).
Circulation
|April 20, 2018
概括
在心力衰竭 (HF) 中蛋白酸酶1 (PP1) 相互作用的变化. 包括Ppp1r7在内的关键相互作用因子与HF进展有关,可能为这种复杂的心脏病提供新的治疗点.
科学领域:
- 心血管生物学
- 分子心脏病学
- 蛋白质组学
背景情况:
- 尽管治疗进展,但心力衰竭的患病率仍在增加.
- 蛋白酶1 (PP1) 在HF病变的作用尚不清楚.
- 之前的研究集中在PP1催化子单元 (PP1c) 上,忽略了它的反应器.
研究的目的:
- 确定心脏PP1相互作用体.
- 测试PP1互动组是否在HF进展过程中重新排列.
- 确定与高频率相关的特定PP1c相互作用体.
主要方法:
- 在小鼠中通过横向大动脉收缩诱导HF.
- PP1c的亲和性净化和质谱测量以确定反应器.
- PP1调节子单元7 (Ppp1r7) 的降低和成像.
主要成果:
- 确定了71个心脏和98个HeLa PP1c相互作用体,形成了最大的PP1相互作用体数据集.
- 包括PP1r7在内的9个PP1c相互作用体显示出与HF进展相关的结合变化.
- 导致心脏功能障碍和释放中断.
结论:
- 在HF进展过程中,PP1相互作用体经历了显著的重组.
- 与HF进展相关的9个关键PP1相互作用体是潜在的治疗点.
- 在HF中,PP1r7可以作为调节PP1相互作用的分子海绵.
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