Mitochondrial nitric oxide metabolism in rat muscle during endotoxemia
Mitochondrial nitric oxide metabolism in rat muscle during endotoxemia
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DOI：
10.1016/j.freeradbiomed.2004.06.034
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发表时间：
2004-11-01
影响因子：
7.4
通讯作者：
Boveris, A
中科院分区：
文献类型：
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作者：
Alvarez, S;Boveris, A
在这项研究中，心脏和隔膜线粒体产生0.69和0.77 nmol一氧化氮（NO）/分钟毫克蛋白，分别占67和24%的最大细胞NO生产率。内毒素血症和感染性休克的发生伴随着损伤组织线粒体的加剧的炎症反应。骨骼肌可能是感染性休克的主要靶器官之一，表现出NO产生增加和早期氧化应激。测定心脏和膈肌线粒体一氧化氮合酶（mtNOS）的动力学特性。对于膈肌，O-2和L-Arg的Km值分别为4.6和37 μ M，心脏的Km值分别为3.3和36 μ M。膈肌和心脏的mtNOS活性最适pH分别为6.5和7.0。内毒素血症大鼠的线粒体一氧化氮合酶活性明显增加，其中隔膜增加90%，心脏增加30%。膈肌和心脏线粒体O-2（.-）和H_2O_2的产生增加2- 3倍，Mn-SOD活性增加2倍，而过氧化氢酶活性无变化。目前对感染性休克的复杂条件下的分子机制的假设之一是，通过mtNOS增强的NO产生导致线粒体基质中过量的过氧亚硝酸盐产生和蛋白质硝化，导致线粒体功能障碍和收缩失败。(C)2004年爱思唯尔公司All rights reserved.
In this study, heart and diaphragm mitochondria produced 0.69 and 0.77 nmol nitric oxide (NO)/min mg protein, rates that account for 67 and 24% of maximal cellular NO production, respectively. Endotoxemia and septic shock occur with an exacerbated inflammatory response that damages tissue mitochondria. Skeletal muscle seems to be one of the main target organs in septic shock, showing an increased NO production and early oxidative stress. The kinetic properties of mitochondrial nitric oxide synthase (mtNOS) of heart and diaphragm were determined. For diaphragm, the Km values for O-2 and L-Arg were 4.6 and 37 muM and for heart were 3.3 and 36 muM. The optimal pH for mtNOS activity was 6.5 for diaphragm and 7.0 for heart. A marked increase in mtNOS activity was observed in endotoxemic rats, 90% in diaphragm and 30% in heart. Diaphragm and heart mitochondrial O-2(.-) and H2O2 production were 2- to 3-fold increased during endotoxemia and Mn-SOD activity showed a 2-fold increase in treated animals, whereas catalase activity was unchanged. One of the current hypotheses for the molecular mechanisms underlying the complex condition of septic shock is that the enhanced NO production by mtNOS leads to excessive peroxynitrite production and protein nitration in the mitochondrial matrix, causing mitochondrial dysfunction and contractile failure. (C) 2004 Elsevier Inc. All rights reserved.