Neuronal Protection by Nitric Oxide-Related Species
As endogenous sources of oxidizing and reducing agents have been discovered, redox modulation of protein function has been recognized to be an important mechanism for many cell types. For our purposes, we confine our review of redox modulation to covalent modification of sulfhydryl (thiol) groups on protein cysteine residues with special reference to the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor in the brain. If the cysteine sulfhydryls possess a sufficient redox potential, oxidizing agents can react to form adducts on single sulfhydryl (thiol, -SH) groups; or if two free sulfhydryl groups are vicinal (in close proximity), disulfide bonds may be formed. Reducing agents can regenerate free sulfhydryl (thiol, -SH) groups by donating electron(s). Considering endogenous redox agents, in addition to the usual suspects including glutathione, ascorbate, vitamin E, lipoic acid, and reactive oxygen species, nitric oxide (NO) and its redox-related species have come to the fore. This has occurred largely because of the rediscovery and application to biological systems of work from the early part of the twentieth century showing the organic synthesis of nitrosothiols (RS-NO) (for review, Stamler et al. 1992). NO group donors represent different redox-related species of the NO group, each with its own distinctive chemistry, that lead to entirely different biological effects. NO-related species include nitric oxide (NO-) but also the other redox-related forms of the NO group: with one less electron (NO+, or nitrosonium ion) or one additional electron (NO-, or nitroxyl anion) (Stamler et al. 1992). Evidence suggests that all three of these redox-related forms or their functional equivalents are important pharmacologically and physiologically, participating in distinctive chemical reactions.
KeywordsNitric Oxide NMDA Receptor NMDA Receptor Activity Redox Modulation Heterolytic Fission
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