Han Jin, Kim Nari, Park Juhee, Seog Dae-Hyun, Joo Hyun, Kim Euiyong
Department of Physiology & Biophysics, College of Medicine, Inje University, Busan, 613-735, Korea.
J Biochem. 2002 May;131(5):721-7. doi: 10.1093/oxfordjournals.jbchem.a003157.
The purpose of this study was to determine whether ATP-sensitive potassium channel (K(ATP) channel) activation generates oxygen free radicals in the rabbit heart. We assayed malondialdehyde (MDA) in rabbit heart slices in vitro as an indicator of oxygen free radical generation. The K(ATP) channel openers, pinacidil and cromakalim, significantly increased MDA production in a concentration-dependent manner. MDA formation also increased linearly with incubation time in the presence of K(ATP) channel openers. The K(ATP) channel blockers, glibenclamide and 5-hydroxydecanoate (5-HD), decreased K(ATP) channel opener-induced MDA formation in a concentration-dependent manner. When Fe(2+) was administered to heart slices that had been pretreated with K(ATP) channel openers, a marked elevation in MDA was observed, compared to heart slices that were treated with Fe(2+) alone. A positive linear correlation between Fe(2+) and MDA level was observed. The MDA levels of heart slices subjected to anoxia for 15 min remained unchanged until reperfusion. When the heart slices were reoxygenated for 30 min, a marked increase in MDA formation was observed. However, in the presence of glibenclamide and 5-HD, reperfusion following anoxia did not result in increased MDA. These results suggest that the opening of mitochondrial K(ATP) channels in rabbit heart slices evokes oxygen free radical generation via a Fenton-type reaction.
本研究的目的是确定ATP敏感性钾通道（K(ATP)通道）激活是否会在兔心脏中产生氧自由基。我们检测了体外兔心脏切片中的丙二醛（MDA），作为氧自由基生成的指标。K(ATP)通道开放剂吡那地尔和克罗卡林以浓度依赖性方式显著增加MDA的产生。在存在K(ATP)通道开放剂的情况下，MDA的形成也随孵育时间呈线性增加。K(ATP)通道阻滞剂格列本脲和5-羟基癸酸（5-HD）以浓度依赖性方式降低K(ATP)通道开放剂诱导的MDA形成。当向预先用K(ATP)通道开放剂处理过的心脏切片中加入Fe(2+)时，与单独用Fe(2+)处理的心脏切片相比，观察到MDA显著升高。观察到Fe(2+)与MDA水平之间呈正线性相关。缺氧15分钟的心脏切片的MDA水平在再灌注前保持不变。当心脏切片再给氧30分钟时，观察到MDA形成显著增加。然而，在存在格列本脲和5-HD的情况下，缺氧后的再灌注并未导致MDA增加。这些结果表明，兔心脏切片中线粒体K(ATP)通道的开放通过芬顿型反应引发氧自由基的产生。
