Redox signaling.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have recently been shown to be involved in a multiplicity of physiological responses through modulation of signaling pathways. Some of the specific signaling components altered by reactive oxygen and nitrogen species (RONS) have begun to be identified. We will discuss RONS signaling by detailing the chemistry of signaling, the roles of antioxidant enzymes as signaling components, thiol chemistry in the specificity of RONS signaling, .NO-heme interactions, and some do's and don'ts of redox signal research. The principal points raised are that: (1) as with classic signaling pathways, signaling by RONS is regulated; (2) antioxidant enzymes are essential 'turn-off components in signaling; (3) spatial relationships are probably more important in RONS signaling than the overall 'redox state' of the cell; (4) deprotonation of cysteines to form the thiolate, which can react with RONS, occurs in specific protein sites providing specificity in signaling; (5) although multiple chemical mechanisms exist for producing nitrosothiols, their formation in vivo remains unclear; and (6) caution should be taken in the use of 'antioxidants' in signal transduction.