Takehara Y, Nakahara H, Inai Y, Yabuki M, Hamazaki K, Yoshioka T, Inoue M, Horton A A, Utsumi K
Institute of Medical Science, Center for Adult Diseases, Kurashiki, Japan.
Cell Struct Funct. 1996 Aug;21(4):251-8. doi: 10.1247/csf.21.251.
Effects of nitric oxide (NO) and NO generating agents, on the electron transport system of mitochondria were examined in a study of the mechanism and physiological importance of NO in energy metabolism. In the presence of various substrates, uncoupled respiration was inhibited by NO in manner which was both dose- and oxygen tension-dependent. Simultaneously measuring changes in cytochrome absorption spectra and respiration showed that the site of action of NO is cytochrome oxidase. Similar inhibition was also brought about by 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene (NOC 18), an NO donor. Electron paramagnetic resonance (EPR) analysis revealed that inhibition of uncoupled respiration occurred only during the presence of NO in the reaction mixture. The inhibitory effect of NO was increased significantly by lowering the concentration of mitochondrial protein. No appreciable inhibition of respiration was observed in the presence of 3-morpholinosydnonimine (SIN-1), a peroxynitrite anion (ONOO-) generating reagent, but inhibition did occur in the presence of superoxide dismutase (SOD). These results indicate that NO reversibly interacts with mitochondria at complex IV thereby inhibiting respiration particularly under physiologically low oxygen tension and that de novo generated ONOO may have no significant effect under the present experimental conditions.
在一项关于一氧化氮（NO）在能量代谢中的作用机制及生理重要性的研究中，检测了NO及NO生成剂对线粒体电子传递系统的影响。在存在各种底物的情况下，NO以剂量和氧张力依赖性的方式抑制解偶联呼吸。同时测量细胞色素吸收光谱和呼吸变化表明，NO的作用位点是细胞色素氧化酶。NO供体1-羟基-2-氧代-3,3-双（2-氨基乙基）-1-三氮烯（NOC 18）也产生类似的抑制作用。电子顺磁共振（EPR）分析显示，仅在反应混合物中存在NO时才会发生对解偶联呼吸的抑制。降低线粒体蛋白浓度会显著增强NO的抑制作用。在过氧亚硝酸盐阴离子（ONOO-）生成试剂3-吗啉代 sydnonimine（SIN-1）存在的情况下未观察到明显的呼吸抑制，但在超氧化物歧化酶（SOD）存在的情况下确实发生了抑制。这些结果表明，NO在复合体IV处与线粒体可逆性相互作用，从而抑制呼吸，特别是在生理低氧张力下，并且在当前实验条件下新生成的ONOO可能没有显著影响。
