A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds

来自 Springer

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298

作者：

SA Lipton，YB Choi，ZH Pan，SZ Lei，HSV Chen，NJ Sucher，J Loscalzo，DJ Singel，JS Stamler

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摘要：

CONGENERS of nitrogen monoxide (NO) are neuroprotective and neurodestructive 1–7. 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 neurotoxicity 3,4 . 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 site 1 . 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.

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关键词：

Brain Neurons Cells, Cultured Animals Rats Nitroprusside Nitrates Superoxides Free Radicals Nitric Oxide