SIN 1 RELEASES NITRIC OXIDE IN PRESENCE OF ELECTRON ACCEPTORS

SIN 1 在电子受体存在下释放一氧化氮

• 批准号: 6279853
• 负责人: JOY JOSEPH
• 金额: $ 0.1万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6279853
• 关键词: animal tissue; bioengineering /biomedical engineering; biological products; biomaterials; biomedical resource

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 imino 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. Consistent with these findings, Pfeiffer et al. have shown an elevation of cGMP levels in endothelial cells when incubated with SIN-1 and NNO (FRBM 22:787-794, 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 electron 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.

SIN-1已被用作产生 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将氧气还原为 单电子转移反应，得到超氧化物和SIN-1阳离子 激进 这种自由基分解形成SIN-1C和一氧化氮。 最后一步是一氧化氮和 过氧化物。 产生过亚硝酸盐。 这一机制表明，在 除了氧之外电子受体SIN-1的存在可以 转化为一氧化氮供体 在这里，我们证明， 一氧化氮陷阱，硝酰基氮氧化物（NNO）能够作为一个 SIN-1的氧化剂。 NNO转化为亚氨基氮氧化物（INO） 当与SIN-1孵育时，如通过ESR监测的。 此外， 还原为羟胺，加入再生的铁氰化物 ESR信号。 当NNO转化为INO后， 通过化学发光在顶空中检测。 符合这些 Pfeiffer等人的研究结果表明， 当内皮细胞与SIN-1和NNO一起孵育时（FRBM 22：787-794， 1997年）。 生物氧化剂如铁细胞色素-C也 刺激SIN-1产生一氧化氮。 此外，本发明还提供了一种方法， SIN-1被肝、肾和心脏的匀浆分解 组织形成一氧化氮。 我们的研究结果表明SIN-1可以 优先与血红素蛋白和其他电子受体反应 在生物系统中产生一氧化氮。 作为氧 组织和细胞中的浓度相对较低，SIN-1反应 与其他生物电子受体，而不是与氧气。 通过 在这种机制下，SIN-1成为一氧化氮供体， 过氧亚硝酸盐介导的氧化。 这或许可以解释 SIN-1在生物系统中的作用