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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Anions / metabolism
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Cells, Cultured
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Cerebral Cortex / cytology
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Female
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N-Methylaspartate / pharmacology
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Neurons / metabolism
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Neurotoxins / metabolism*
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Nitric Oxide / pharmacology
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Nitric Oxide Donors / pharmacology
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Nitric Oxide Synthase / metabolism
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Nitrogen Oxides / metabolism*
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Oocytes
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate / chemistry
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Receptors, N-Methyl-D-Aspartate / physiology
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Sulfhydryl Compounds / chemistry
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Sulfhydryl Compounds / metabolism
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Xenopus laevis
Substances
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Anions
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Neurotoxins
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Nitric Oxide Donors
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Nitrogen Oxides
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Receptors, N-Methyl-D-Aspartate
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Sulfhydryl Compounds
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Nitric Oxide
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N-Methylaspartate
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Nitric Oxide Synthase
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nitroxyl