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.
authors.affiliation: Cerebrovascular and NeuroScience Research Institute, Brigham and Women's Hospital and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: W K
authors.initials: WK
authors.lastname: Kim
authors.forename: Y B
authors.initials: YB
authors.lastname: Choi
authors.forename: P V
authors.initials: PV
authors.lastname: Rayudu
authors.forename: P
authors.initials: P
authors.lastname: Das
authors.forename: W
authors.initials: W
authors.lastname: Asaad
authors.forename: D R
authors.initials: DR
authors.lastname: Arnelle
authors.forename: J S
authors.initials: JS
authors.lastname: Stamler
authors.forename: S A
authors.initials: SA
authors.lastname: Lipton
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005260:Female; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009589:Nitrogen Oxides / Q000378:metabolism*; D009865:Oocytes; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D000838:Anions; D009498:Neurotoxins; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D016194:Receptors, N-Methyl-D-Aspartate; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; C039900:nitroxyl