Transduction of Redox Signaling by Electrophile-Protein Reactions
Tanja K. Rudolph1,2 and
Bruce A. Freeman1*
1 Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
2 Department of Cardiology, University Heart Center Hamburg, Hamburg, Germany.
Gloss: Chemically reactive by-products of cellular redox reactions are frequently thought to induce deleterious actions. However, not all redox-mediated modifications are harmful; some have important physiological consequences. Some posttranslational protein modifications that are induced by electrophilic products of redox reactions may modulate physiological signaling pathways that have evolved to act as sensors of oxidative conditions. Additional insight into specific biological targets of electrophiles and the regulation of their reactions can reveal new therapeutic strategies for treating pain, acute and chronic inflammatory injury, and metabolic diseases. This Review with 4 figures, 2 tables, and 148 references describes biologically important electrophiles, methods for detecting proteins modified by these electrophilic compounds and the cellular consequences of this type of posttranslational modification.
* Corresponding author. E-mail, freerad{at}pitt.edu