title: Chemical approaches to discovery and study of sources and targets of hydrogen peroxide redox signaling through NADPH oxidase proteins.
abstract: Hydrogen peroxide (H2O2) is a prime member of the reactive oxygen species (ROS) family of molecules produced during normal cell function and in response to various stimuli, but if left unchecked, it can inflict oxidative damage on all types of biological macromolecules and lead to cell death. In this context, a major source of H2O2 for redox signaling purposes is the NADPH oxidase (Nox) family of enzymes, which were classically studied for their roles in phagocytic immune response but have now been found to exist in virtually all mammalian cell types in various isoforms with distinct tissue and subcellular localizations. Downstream of this tightly regulated ROS generation, site-specific, reversible covalent modification of proteins, particularly oxidation of cysteine thiols to sulfenic acids, represents a prominent posttranslational modification akin to phosphorylation as an emerging molecular mechanism for transforming an oxidant signal into a dynamic biological response. We review two complementary types of chemical tools that enable (a) specific detection of H2O2 generated at its sources and (b) mapping of sulfenic acid posttranslational modification targets that mediate its signaling functions, which can be used to study this important chemical signal in biological systems.
authors.affiliation: Department of Chemistry.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Brewer
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Garcia
authors.forename: Carl S
authors.initials: CS
authors.lastname: Onak
authors.forename: Kate S
authors.initials: KS
authors.lastname: Carroll
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Chang
mesh_terms: D000818:Animals; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D010084:Oxidation-Reduction; D015398:Signal Transduction; D013434:Sulfenic Acids / Q000378:metabolism
chemical_list: D013434:Sulfenic Acids; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases
keywords: bioorthogonal chemistry; fluorescent probes; molecular imaging; oxidative stress; posttranslational modifications; reactive oxygen species