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 journalArticle

177 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 1
Externally publishedYes

Fingerprint

N-Methyl-D-Aspartate Receptors
Nitric Oxide Synthase
Anions
S-Nitrosothiols
Superoxide Dismutase
Oxidation-Reduction
Hemoglobins
Down-Regulation
Metals
Brain
Proteins
nitroxyl
Neuroprotection

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kim, W-K., Choi, Y. B., Rayudu, P. V., Das, P., Asaad, W., Arnelle, D. R., ... Lipton, S. A. (1999). Attenuation of NMDA receptor activity and neurotoxicity by nitroxyl anion, NO- Neuron, 24(2), 461-469. https://doi.org/10.1016/S0896-6273(00)80859-4

Attenuation of NMDA receptor activity and neurotoxicity by nitroxyl anion, NO- . / Kim, Won-Ki; Choi, Yun Beom; Rayudu, Posina V.; Das, Prajnan; Asaad, Wael; Arnelle, Derrick R.; Stamler, Jonathan S.; Lipton, Stuart A.

In: Neuron, Vol. 24, No. 2, 01.10.1999, p. 461-469.

Research output: Contribution to journalArticle

Kim, W-K, Choi, YB, Rayudu, PV, Das, P, Asaad, W, Arnelle, DR, Stamler, JS & Lipton, SA 1999, 'Attenuation of NMDA receptor activity and neurotoxicity by nitroxyl anion, NO- ', Neuron, vol. 24, no. 2, pp. 461-469. https://doi.org/10.1016/S0896-6273(00)80859-4
Kim, Won-Ki ; Choi, Yun Beom ; Rayudu, Posina V. ; Das, Prajnan ; Asaad, Wael ; Arnelle, Derrick R. ; Stamler, Jonathan S. ; Lipton, Stuart A. / Attenuation of NMDA receptor activity and neurotoxicity by nitroxyl anion, NO- In: Neuron. 1999 ; Vol. 24, No. 2. pp. 461-469.
@article{6dffd7d9892e428893aa01bb93d088a0,
title = "Attenuation of NMDA receptor activity and neurotoxicity by nitroxyl anion, NO-",
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.",
author = "Won-Ki Kim and Choi, {Yun Beom} and Rayudu, {Posina V.} and Prajnan Das and Wael Asaad and Arnelle, {Derrick R.} and Stamler, {Jonathan S.} and Lipton, {Stuart A.}",
year = "1999",
month = "10",
day = "1",
doi = "10.1016/S0896-6273(00)80859-4",
language = "English",
volume = "24",
pages = "461--469",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Attenuation of NMDA receptor activity and neurotoxicity by nitroxyl anion, NO-

AU - Kim, Won-Ki

AU - Choi, Yun Beom

AU - Rayudu, Posina V.

AU - Das, Prajnan

AU - Asaad, Wael

AU - Arnelle, Derrick R.

AU - Stamler, Jonathan S.

AU - Lipton, Stuart A.

PY - 1999/10/1

Y1 - 1999/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033213383&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033213383&partnerID=8YFLogxK

U2 - 10.1016/S0896-6273(00)80859-4

DO - 10.1016/S0896-6273(00)80859-4

M3 - Article

VL - 24

SP - 461

EP - 469

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 2

ER -