Neither Nitrite Nor Nitric Oxide Mediate Toxic Effects of Nitroglycerin on Mitochondria
Neither Nitrite Nor Nitric Oxide Mediate Toxic Effects of Nitroglycerin on Mitochondria
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DOI：
10.1002/jbt.20389
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发表时间：
2011-09-01
影响因子：
3.6
通讯作者：
Kozlov, Andrey V.
中科院分区：
文献类型：
--
作者：
Dungel, Peter;Haindl, Susanne;Kozlov, Andrey V.
硝酸甘油（NG）的主要作用是通过乙醛脱氢酶2（ALDH 2）催化释放一氧化氮（NO）来实现的。此外，已显示NG抑制线粒体呼吸。本研究的目的是澄清是否NG介导的线粒体呼吸抑制是由NO介导的。在大鼠肝线粒体中，NG抑制复合物I依赖的呼吸和诱导活性氧（ROS）的产生，优先在复合物I。这两种作用对ALDH 2抑制剂水合氯醛不敏感。亚硝酸盐，NG中间体，没有影响线粒体呼吸或ROS的产生。NO优先抑制复合物I，但不提高ROS的产生。而NO清除剂血红蛋白和蓝光对NO或NG抑制的线粒体有相反的作用。总之，我们的数据表明，虽然NG通过NO释放诱导血管舒张，但它通过NO非依赖性途径引起线粒体功能障碍。(C)2011 Wiley Periodicals，Inc. J Biochem Mol Toxicol 25：297-302，2011;在wileyonlinelibrary.com在线查看这篇文章。DOI 10：1002/jbt.20389
It is commonly accepted that the major effect of nitroglycerin (NG) is realized through the release of nitric oxide (NO) catalyzed by aldehyde dehydrogenase-2 (ALDH2). In addition, it has been shown that NG inhibits mitochondrial respiration. The aim of this study was to clarify whether NG-mediated inhibition of mitochondrial respiration is mediated by NO. In rat liver mitochondria, NG inhibited complex-I-dependent respiration and induced reactive oxygen species (ROS) production, preferentially at complex I. Both effects were insensitive to chloral hydrate, an ALDH2 inhibitor. Nitrite, an NG intermediate, had no influence on either mitochondrial respiration or the production of ROS. NO inhibited preferentially complex I but did not elevate ROS production. Hemoglobin, an NO scavenger, and blue light had contrary effects on mitochondria inhibited by NO or NG. In summary, our data suggest that although NG induces vasodilatation via NO release, it causes mitochondrial dysfunction via an NO-independent pathway. (C) 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:297-302, 2011; View this article online at wileyonlinelibrary.com. DOI 10:1002/jbt.20389