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

Recent evidence indicates that the NO-related species, nitroxyl anion (NO-) , is produced in physiological systems by several redox metal-containing pr oteins, including hemoglobin, nitric oxide synthase (NOS), superoxide dismu tase, and S-nitrosothiols (SNOs), which have recently been identified in br ain. However, the chemical biology of NO- remains largely unknown. Here, we show that NO--unlike NO., but reminiscent of NO+ transfer (or S-nitrosylat ion) - reacts mainly with Cys-399 in the NR2A subunit of the N-methyl-D-asp artate (NMDA) receptor to curtail excessive Ca2+ influx and thus provide ne uroprotection from excitotoxic insults. This effect of NO- closely resemble s that of NOS, which also downregulates NMDA receptor activity under simila r conditions in culture.