Attenuation of NMDA receptor activity and neurotoxicity by nitroxyl anion, NO- |
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Authors: | Kim W K Choi Y B Rayudu P V Das P Asaad W Arnelle D R Stamler J S Lipton S A |
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Affiliation: | Cerebrovascular and NeuroScience Research Institute, Brigham and Women's Hospital and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA. |
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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. |
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