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氨酸启动了线粒体ATP敏感通道的开放:在缺血预先调节中的关键步骤?
1Institute of Molecular Cardiobiology, Johns Hopkins University, Baltimore, MD 21205, USA.
Circulation
|August 16, 2000
概括
腺素主要通过蛋白激酶C为心脏保护的线粒体K (((ATP) 通道.这解释了腺是如何启动缺血预先调节的,并将级联中的关键元素连接起来.
科学领域:
- 心血管生理学心血管生理学
- 线粒体生物学 线粒体生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 氨酸启动缺血预调,这是对心脏损伤的保护现象.
- 线粒体ATP敏感 (K(ATP)) 通道被认为是预先调节的关键效应因素.
- 腺和线粒体K ((ATP) 通道之间的精确机械联系仍然需要阐明.
研究的目的:
- 在缺血性预约的背景下,确定腺和线粒体K ((ATP) 通道之间的机械相互作用.
- 研究蛋白质激酶C在调解腺对线粒体K ((ATP) 通道的影响中的作用.
主要方法:
- 线粒体K ((ATP) 通道活性在子心室肌细胞中使用氧化物诱导的黄蛋白氧化来量化.
- 对腺素对道活性的影响在受体对抗剂和激酶抑制剂的存在和缺乏的情况下进行了评估.
- 在模拟性缺血模型中评估了心脏保护作用,干预措施被特定的K ((ATP)) 通道阻断剂阻断.
主要成果:
- 腺素 (100μmol/L) 增加了线粒体K(ATP) 通道活性,并减少了对开放的延迟.
- 这些效应被腺受体对抗剂8-(p-sulfophenyl) -theophylline和蛋白质激酶C抑制剂polymyxin B.消除了.
- 氨酸缓解模拟性缺血诱导的细胞损伤,这种效应被线粒体K ((ATP) 通道阻断剂5-基二甲酸阻断,但不是HMR1098.
结论:
- 氨酸受体激活使线粒体K (((ATP) 通道以蛋白质激酶C依赖的方式开放.
- 这些发现在心脏保护中建立了腺信号传递和线粒体K ((ATP) 通道功能之间的直接联系.
- 这项研究阐明了缺血预条件级联中的关键分子事件.
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