Attenuation of NMDA receptor activity and neurotoxicity by nitroxyl anion, NO-

Won Ki Kim, Yun Beom Choi, Posina V. Rayudu, Prajnan Das, Wael Asaad, Derrick R. Arnelle, Jonathan S. Stamler, Stuart A. Lipton

Research output: Contribution to journalArticlepeer-review

180 Citations (Scopus)

Abstract

Recent evidence indicates that the NO-related species, nitroxyl anion (NO-), is produced in physiological systems by several redox metal- containing proteins, including hemoglobin, nitric oxide synthase (NOS), superoxide dismutase, and S-nitrosothiols (SNOs), which have recently been identified in brain. However, the chemical biology of NO- remains largely unknown. Here, we show that NO- - unlike NO-, but reminiscent of NO+ transfer (or S-nitrosylation) - reacts mainly with Cys-399 in the NR2A subunit of the N-methyl-D-aspartate (NMDA) receptor to curtail excessive CA2+ influx and thus provide neuroprotection from excitotoxic insults. This effect of NO- closely resembles that of NOS, which also downregulates NMDA receptor activity under similar conditions in culture.

Original languageEnglish
Pages (from-to)461-469
Number of pages9
JournalNeuron
Volume24
Issue number2
DOIs
Publication statusPublished - 1999 Oct
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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