FIG. 2.

Reactive oxygen species (ROS) and HNO interaction with thiols. Thiols, and in particular reactive cysteines, are subjected to a continuum of modifications by ROS and HNO. HNO can modify cysteines in two distinct ways. The first is via its direct targeting of reactive thiols in cysteine residues to form N-hydroxysulfenamide (RSNHOH). Second, if there is an additional available thiol in the vicinity, a disulfide bond may form. Whether the formation of sulfenamide always leads to irreversible and likely pathological signaling remains to be fully established. Conversely, it is plausible that HNO acting as a mild oxidizing agent promotes the formation of reversible inter- and/or intradisulfide bonds that ultimately leads to changes in protein function (see also text). (To see this illustration in color the reader is referred to the web version of this article at www.liebertonline.com/ars).