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: 6118834
• 负责人: JOY JOSEPH
• 金额: $ 0.16万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6118834
• 关键词: animal tissue; bioengineering /biomedical engineering; biological products; biomaterials; biomedical resource; enzymes; proteins

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.

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，得到过氧亚硝酸盐。 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转化为氨基氮氧自由基（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。 Consis帐篷， Pfeiffer等人的研究结果表明， 当与SIN-1和NNO孵育时， （FRBM22：787-794，1997）。 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，SIN-1被肝匀浆分解， 肾脏和心脏组织形成一氧化氮。 我们的研究结果表明 SIN-1可以优先与血红素蛋白和其他 电子受体在生物系统中产生一氧化氮。 作为 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， 可以抑制过氧亚硝基介导的氧化。 这可以解释 SIN-1在生物系统中的矛盾作用。