神经元氧化合成酶的条件过度表达在缺血症/再输血中具有心脏保护作用
Natalie Burkard1, Tatjana Williams, Martin Czolbe
1Department of Medicine I, University of Wuerzburg, Oberduerrbacherstrasse 6, Wuerzburg, Germany.
Circulation
|October 6, 2010
概括
过度表达神经元氧化合成酶 (nNOS) 通过减少反应性氧物种和抑制线粒体功能来保护心脏免受缺血/反损伤,从而降低氧气消耗.
科学领域:
- 心血管研究研究心血管研究
- 线粒体生物学 线粒体生物学
- 氧化信号传输 氧化信号传输
背景情况:
- 神经氧化合成酶 (nNOS) 的过度表达以前抑制了L型Ca2+通道,并降低了心肌收缩性.
- nNOS在心脏肌细胞内具有多个细胞内点.
- 研究了nNOS在缺血/反损伤期间的心脏保护作用,假设线粒体和活性氧物种 (ROS) 调制.
研究的目的:
- 为了研究在缺血/反 (I/R) 损伤后的nNOS过度表达的心脏保护机制.
- 确定线粒体功能和ROS生成在nNOS介导心脏保护中的作用.
主要方法:
- 使用了具有条件nNOS过度表达的转基因小鼠.
- 在野生型和nNOS过度表达的小鼠中诱导I/R损伤.
- 使用隔离的心脏和心肌条纹评估线粒体功能,ROS水平,心脏病发作大小和nNOS局部化.
- 研究了热冲击蛋白90在nNOS线粒体转移中的作用.
主要成果:
- 在I/R损伤和转基因小鼠中心脏线粒体中积累的nNOS.
- nNOS线粒体转移取决于热冲击蛋白90.
- nNOS过度表达显著减少了心脏病发作的大小,并在隔离的心脏中显示出心脏保护作用.
- 线粒体酸盐水平增加,而细胞染色体c氧化酶活性随着nNOS过度表达而降低.
- 心肌的氧气消耗减少了,并且在nNOS过度表达的小鼠中,ROS度显著下降.
结论:
- 有条件的转基因nNOS过度表达可以保护肌肉细胞免受I/R损伤.
- 心脏保护与减少ROS生成和酸盐介导的线粒体功能的抑制有关.
- 在基线条件下心肌氧消耗的减少有助于观察到的心脏保护作用.
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