· NO,RSNO,ONOO -,NO +,· NOO,NOx-Dynamic Regulation of Oxidant Scavenging,Nitric Oxide Stores,and Cyclic GMP-Independent Cell Signaling

Abstract

Following its release from nitric oxide synthase, nitric oxide seldom perfuses the cytosol; rather this reactive mediator quickly interacts with available target molecules proximate to its site of release. Within the cell, virtually every component, low-molecular-weight oxidants and reductants, proteins, lipids, sugars, and nucleic acids can be modified by nitrogen oxides thus acting as potential targets for reactive nitrogen oxides. Adducts formed by nitrogen oxides often modulate the cellular activities of the target molecules, and these modified molecules may be differentially metabolized or localized. The formation of nitrogen oxide adducts can be a reversible process, and the reactive nitrogen species released may be specifically oxidized or reduced during the process. Recently, numerous studies have demonstrated that reversible nitration of cellular proteins acts to transduce molecular signals regulating such diverse processes as muscle contraction, neurotransmission, protein metabolism, and apoptosis. The vast numbers of molecules that undergo biologically relevant interactions with nitrogen oxides imply that the cellular concentration of nitrosated and nitrated species may effectively comprise a reserve or cellular store. Potentially, these nitroso reserves function as critical components of the overall redox status of the intracellular environs. Understanding the dynamic regulation of nitric oxide/nitrogen oxides release from these stores is likely to provide clues important in resolving the complex pathophysiology of poorly understood multifactorial disorders, including neurodegeneration, multiorgan failure, cardiomyopathy, and septic shock.