Regulation of cell processes by rective oxygen and nitric oxide species - Mechanisms of reactions

Abstract

Recent evidence revealed that reactive oxygen species (ROS) such assuperoxide (O ) and hydrogen peroxide (H O ), which are conventionally2.-22viewed as unwanted and toxic by-products of life in an aerobic environment,have physiological roles. Appraisal of the roles of reactive NO species(RNOS), such as nitrosonium (NO ) and nitroxyl (NO ) ions, peroxynitrite+-(OONO ), and higher nitrogen oxides (NO ) in NO mediated processes, is-xgrowing at a rapid rate. ROS and RNOS may evoke a variety of cellularresponses, ranging from major changes in mammalian cell gene expressionto apoptotic death. The greater prevalence and reactivity of thiols over otherbiological nucleophiles makes them targets for both ROS and RNOS. Anyessential protein containing cysteine residue that is strategically located ateither active or allosteric site should be considered as a target for regulationby ROS and/or RNOS. Candidate molecules include proteins that are themselves involved in signal transduction processes, ion channels, receptors,G-proteins, protein-kinases, protein phosphatases, and transcription-activatingfactors. In this paper the mechanisms of generation of ROS and RNOS andtheir reactions with thiols are briefly described. The regulation of cellprocesses by ROS and RNOS is illustrated by the interference of ROS andRNOS effects with receptor tyrosine kinases signaling.