Hydrogen peroxide and peroxiredoxins in redox regulation of intracellular signaling

A growing body of evidence indicates that hydrogen peroxide is generated in response to ligand-receptor interaction and is involved in redox-regulation of signaling pathways in various cell types. The mechanism of redox-regulation is based on post-translational modification of key regulatory proteins that contain essential cysteinyl residues at their catalytic sites. Hydrogen peroxide acts as a chemical mediator that affects signaling through reversible oxidation of thiol groups of essential cysteins, which results in changes in protein catalytic activity. The accumulation and propagation of H2O2 signal in a cell is regulated by antioxidant proteins peroxiredoxins. The catalytic cycle of peroxiredoxins enables them to keep a low resting level of H2O2 in a cell, while the hyperoxidation-reduction cycle allows for H2O2 bursts during signal transduction. H2O2, being a small, diffusible, highly reactive molecule generated and destroyed in enzymatic reactions and capable of regulating the phosphorylation-dephosphorylation events in a cell, meets all major criteria of the second messenger in signal transduction but the criterion of specificity. How a toxic molecule that is potentially dangerous to all biomolecules in a cell can specifically relay information through signaling cascades is discussed in this review.