通过乙转移酶p300进行适应性心脏缩的定量控制
Jian Qin Wei1, Lina A Shehadeh, James M Mitrani
1University of Miami School of Medicine, Department of Molecular and Cellular Pharmacology, Miami, FL, USA.
Circulation
|August 14, 2008
概括
乙转移酶p300的微小增加足以导致心肌生长 (心肌缩). 这种蛋白质对适应性心脏生长至关重要,可能是治疗心力衰竭的目标.
科学领域:
- 心血管生物学 心血管生物学
- 分子心脏病学分子心脏病学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 乙转移酶p300 (p300) 对于心脏发育至关重要.
- 通过MEF2和GATA4转录,p300与心脏肌细胞生长有关.
- 对于p300在调节心脏生长中的体内作用仍然不清楚.
研究的目的:
- 在体内调查p300在心脏缩中的作用.
- 为了确定p300水平是否会影响应对压力的心脏生长.
主要方法:
- 使用了具有不同p300表达水平的小鼠模型.
- 通过横向大动脉凝结 (压力过载) 诱导的心脏缩.
- 评估心脏质量,死亡率,基因素脱乙酶活性和基质乙化.
主要成果:
- 随着压力过载,产后生长和心力衰竭,p300水平显著增加.
- 最小的p300过度表达导致了相当大的心脏缩;剂量与死亡率和心脏质量相关.
- 降低p300水平 (异合性损失) 降低了50%的过度缩,并挽救了p300过度表达的表型.
- 增加的p300活性与基因素3,GATA-4和MEF2.2的乙化相关.
- 在p300转基因心脏中的升级基因被丰富为MEF2结合部位.
结论:
- 对于心肌缩来说,p300的小幅增加是必要的,也是足够的.
- 通过MEF2乙化,p300可能会通过MEF2乙化驱动缩,可能会影响胰岛素脱乙酶活性.
- 在血液动力学压力下,p300的可用性是适应性心脏生长的速度限制因素.
- 减少p300可以缓解过度缩小并防止心力衰竭的进展.
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