SIN 1 RELEASES NITRIC OXIDE IN PRESENCE OF ELECTRON ACCEPTORS

SIN-1已经作为实验工具用于产生 过氧亚硝酸盐。然而，SIN-1的药理活性 类似于一氧化氮供体。SIN-1通过一种 单电子转移反应生成超氧化物和SiN-1阳离子 激进的。这个自由基分解成SIN-1C和一氧化氮。 最后一步是一氧化氮和 产生过氧亚硝酸根的超氧化物。这种机制表明，在 氧以外的电子受体SIN-1的存在可以是 转化为一氧化氮供体。在这里，我们演示了 一氧化氮陷阱，硝基氮氧化物(NNO)能够作为一种 SIN-1的氧化剂。NNO转化为氨基氮氧化物(INO) 当与SIN-1孵育时，通过ESR监测。伊诺更远 还原为羟胺作为添加铁氰化物再生 ESR信号。在NNO转化为INO后，一氧化氮被 通过化学发光法在头部空间检测到。简明的帐篷 这些发现，Pfeiffer等人。显示出cGMP水平的升高 在与SIN-1和NNO孵育时内皮细胞中 (FRBM22：787-794,1997)。生物氧化剂，如 铁细胞色素-C还刺激SIN-1产生一氧化氮。 此外，肝脏匀浆对SIN-1的分解， 肾脏、心脏组织形成一氧化氮。我们的发现表明 SIN-1可以优先与血红素蛋白和其他 生物系统中产生一氧化氮的电子受体。AS 组织和细胞中的氧浓度相对较低，SIN-1 与其他生物电子受体反应，而不是与 氧气。通过这种机制，SIN-1成为一氧化氮供体，并 能抑制过氧亚硝酸根介导的氧化。这可能解释了 SIN-1在生物系统中的悖论效应。

SIN-1 has been used as an experimental tool for the generation of peroxynitrite. However, the pharmacological activity of SIN-1 resembles that of a nitric oxide donor. SIN-1 reduces oxygen by a one-electron transfer reaction to give superoxide and SIN-1 cation radical . This radical decomposes to form SIN-1C and nitric oxide. The last step is the rapid reaction between nitric oxide and superoxide to give peroxynitrite. This mechanism suggests that, in the presence of an electron acceptor other than oxygen, SIN-1 could be converted into a nitric oxide donor. Here we demonstrate that the nitric oxide trap, nitronyl nitroxide (NNO) is able to act as an oxidizing agent for SIN-1. NNO was converted to amino nitroxide (INO) when incubated with SIN-1, as monitored by ESR. INO was further reduced to the hydroxylamine as addition of ferricyanide regenerated the ESR signal. After NNO was converted to INO, nitric oxide was detected in the headspace by chemiluminescence. Consis tent with these findings, Pfeiffer et al. have shown an elevation of cGMP levels in endothelial cells when incubated with SIN-1 and NNO (FRBM22:787-794, 1997). Biological oxidizing agents such as ferricytochrome-c also stimulated nitric oxide production from SIN-1. In addition, decomposition of SIN-1 by the homogenate of liver, kidney, and heart tissues formed nitric oxide. Our findings suggest that SIN-1 could preferentially react with heme proteins and other electon acceptors in biological systems to produce nitric oxide. As the oxygen concentration in tissues and cells is relatively low, SIN-1 reacts with other biological electron acceptors rather than with oxygen. By this mechanism, SIN-1 becomes a nitric oxide donor and could inhibit peroxynitrite-mediated oxidation. This may explain the paradoxical effects of SIN-1 in biological systems.