CONGENERS of nitrogen monoxide (NO) are neuroprotective and neurodestructive1– 7. To address this apparent paradox, we considered the effects on neurons of compounds characterized by alternative redox states of NO: nitric oxide (NO.) and nitrosonium ion (NO+)8. Nitric oxide, generated from NO. donors or synthesized endogenously after NMDA (N-methyl-D-aspartate) receptor activation, can lead to neurotoxicity3,4. Here, we report that NO.-mediated neurotoxicity is engendered, at least in part, by reaction with superoxide anion (O.-2), apparently leading to formation of peroxynitrite (ONOO−), and not by NO. alone. In contrast, the neuroprotective effects of NO result from downregulation of NMDA-receptor activity by reaction with thiol group(s) of the receptor's redox modulatory site1. This reaction is not mediated by NO. itself, but occurs under conditions supporting S-nitrosylation of NMDA receptor thiol (reaction or transfer of NO+). Moreover, the redox versatility of NO allows for its interconversion from neuroprotective to neurotoxic species by a change in the ambient redox milieu. The details of this complex redox chemistry of NO may provide a mechanism for harnessing neuroprotective effects and avoiding neurotoxicity in the central nervous system.

中文翻译：

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一氧化氮和相关亚硝基化合物的神经保护和神经破坏作用的基于氧化还原的机制

一氧化氮 (NO) 的同类物具有神经保护作用和神经破坏作用 1– 7。为了解决这一明显的悖论，我们考虑了以 NO 的替代氧化还原状态为特征的化合物对神经元的影响：一氧化氮 (NO.) 和亚硝基离子 (NO+)8。一氧化氮，由 NO 生成。供体或在 NMDA（N-甲基-D-天冬氨酸）受体激活后内源性合成，可导致神经毒性 3,4。在这里，我们报告说 NO. 介导的神经毒性至少部分是由与超氧阴离子 (O.-2) 反应引起的，显然导致过氧亚硝酸盐 (ONOO-) 的形成，而不是由 NO。独自的。相比之下，NO 的神经保护作用是通过与受体氧化还原调节位点的硫醇基团反应而下调 NMDA 受体活性所致。该反应不是由 NO 介导的。本身，但在支持 NMDA 受体硫醇的 S-亚硝基化（NO+ 的反应或转移）的条件下发生。此外，NO 的氧化还原多功能性允许通过环境氧化还原环境的变化将其从神经保护性物质转化为神经毒性物质。NO 的这种复杂氧化还原化学的细节可能提供一种利用神经保护作用和避免中枢神经系统神经毒性的机制。