Mitochondrial KATP channel opening protects a human atrial-derived cell line by a mechanism involving free radical generation
Mitochondrial KATP channel opening protects a human atrial-derived cell line by a mechanism involving free radical generation
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DOI：
10.1016/s0008-6363(01)00330-3
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发表时间：
2001-09-01
影响因子：
10.8
通讯作者：
Yellon, DM
中科院分区：
文献类型：
--
作者：
Carroll, R;Gant, VA;Yellon, DM
目的：线粒体K-ATP通道开放剂对缺血/再灌注损伤的保护机制仍有争议。有证据表明，这些通道的打开可能通过触发机制起作用，而不仅仅是末端效应器。我们研究了线粒体K-ATP通道开放剂二氮嗪对线粒体功能参数的影响，特别是在模拟缺血/再灌注（LSI/R）的人心房衍生细胞系模型中活性氧（ROS）的产生。方法和结果：使用碘化丙啶（PI）排除法评估生存率。二氮嗪治疗可提供针对LSI/R的保护（13.9 +/-0.9% vs. 36.9 +/-4.5%对照），而mitoK（ATP）通道阻断剂5-羟基癸酸酯（5-HD）（33.3 +/-3.6%）和自由基清除剂2-巯基丙酰甘氨酸（MPG）（29 +/-4.0%）预处理可消除该保护。二氮嗪导致ROS探针氧化增加，线粒体示踪剂橙子减少（1.3对1.0任意单位对照; P
Objectives: The mechanism by which the mitochondrial K-ATP channel openers confer protection against ischemia/reperfusion injury is debated. Evidence suggests that rather than solely being an end effector, opening of these channels may act by a trigger mechanism. We examined the effects of the mitochondrial K-ATP channel opener, diazoxide on parameters of mitochondrial function with specific reference to reactive oxygen species (ROS) generation in a human atrial derived cell line model of simulated ischemia/reperfusion (LSI/R). Methods and results: Propidium iodide (PI) exclusion was used to assess survival. Diazoxide treatment conferred protection against LSI/R ( 13.9 +/-0.9% vs. 36.9 +/-4.5% controls) that was abolished by pre-treatment with the mitoK(ATP) channel blocker, 5-hydroxydecanoate (5-HD) (33.3 +/-3.6%) and with the free radical scavenger, 2-mercaptopropionylglycine (MPG) (29 +/-4.0%). Diazoxide caused increased oxidation of the ROS probe, reduced mitotracker orange (1.3 vs. 1.0 arbitrary units for control; P