Mitochondrial nitrite reduction coupled to soluble guanylate cyclase activation: Lack of evidence for a role in the bioactivation of nitroglycerin
Mitochondrial nitrite reduction coupled to soluble guanylate cyclase activation: Lack of evidence for a role in the bioactivation of nitroglycerin
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DOI：
10.1016/j.niox.2008.09.003
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发表时间：
2009-02-01
影响因子：
3.9
通讯作者：
Mayer, Bernd
中科院分区：
文献类型：
--
作者：
Kollau, Alexander;Beretta, Matteo;Mayer, Bernd
线粒体呼吸链的组分将亚硝酸盐还原为一氧化氮（NO），可能将线粒体醛脱氢酶（ALDH2）的硝化甘油生物转化与可溶性鸟苷酸环化酶（sGC）的激活联系起来。我们用纯化的sGC作为检测分离的心脏和肝脏线粒体亚硝酸盐和GTN产生的no样生物活性的检测器。外源性NADH引起氧消耗的显著增加，而这种增加被粘噻唑和氰化物完全抑制。NADH对心肌线粒体的耗氧伴随着sGC的激活和NO对氰化物的敏感形成。硝酸甘油的线粒体生物转化对ALDH2抑制剂敏感，并与sGC激活偶联，但不受呼吸底物或抑制剂的影响。我们的数据表明，细胞色素c氧化酶在低O-2张力下催化亚硝酸盐还原为NO，但反对该途径参与硝化甘油的线粒体生物活化。(c) 2008爱思唯尔公司版权所有。
Reduction of nitrite to nitric oxide (NO) by components of the mitochondrial respiratory chain may link nitroglycerin biotransformation by mitochondrial aldehyde dehydrogenase (ALDH2) to activation of soluble guanylate cyclase (sGC). We used purified sGC as detector for NO-like bioactivity generated from nitrite and GTN by isolated heart and liver mitochondria. Exogenous NADH caused a pronounced increase in oxygen consumption that was completely inhibited by myxothiazol and cyanide. Oxygen depletion of cardiac mitochondria by NADH was accompanied by activation of sGC and cyanide-sensitive formation of NO. Mitochondrial biotransformation of nitroglycerin was sensitive to ALDH2 inhibitors and coupled to sGC activation but not affected by respiratory substrates or inhibitors. Our data suggest that cytochrome c oxidase catalyzes reduction of nitrite to NO at low O-2 tension but argue against the involvement of this pathway in mitochondrial bioactivation of nitroglycerin. (c) 2008 Elsevier Inc. All rights reserved.