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

186 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

Bibliographical note

Funding Information:
This work was supported in part by NIH grants from the National Eye Institute (R01 EY05477 and R01 EY09024 to S. A. L.), the National Institute of Child Health and Human Development (P01 HD29587 to S. A. L.), and the National Heart, Lung, and Blood Institute (R01 HL52529 and HL59130 to J. S. S.). S. A. L. was a consultant to and received sponsored research support from Neurobiological Technologies (Richmond, CA) and Allergan (Irvine, CA) in the field of NMDA receptor antagonists.

ASJC Scopus subject areas

  • General Neuroscience

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