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.
Bibliographical noteFunding Information:
This work was supported in part by NIH grants from the National Eye Institute (R01 EY05477 and R01 EY09024 to S. A. L.), the National Institute of Child Health and Human Development (P01 HD29587 to S. A. L.), and the National Heart, Lung, and Blood Institute (R01 HL52529 and HL59130 to J. S. S.). S. A. L. was a consultant to and received sponsored research support from Neurobiological Technologies (Richmond, CA) and Allergan (Irvine, CA) in the field of NMDA receptor antagonists.
ASJC Scopus subject areas
- General Neuroscience