An unexplored role for Peroxiredoxin in exercise-induced redox signalling?

• Peroxiredoxin (PRDX) has a very high affinity for hydrogen peroxide (H2O2).
• H2O2 may have a role in tissue remodelling following exercise.
• Acute exercise can cause the oxidation of PRDX in human blood cells.
• PRDX can form disulphide bridges with proteins implicated with exercise adaption.
• PRDX may be an important regulator of redox pathways following exercise.

Peroxiredoxin (PRDX) is a ubiquitous oxidoreductase protein with a conserved ionised thiol that permits catalysis of hydrogen peroxide (H2O2) up to a million times faster than any thiol-containing signalling protein. The increased production of H2O2 within active tissues during exercise is thought to oxidise conserved cysteine thiols, which may in turn facilitate a wide variety of physiological adaptations. The precise mechanisms linking H2O2 with the oxidation of signalling thiol proteins (phosphates, kinases and transcription factors) are unclear due to these proteins' low reactivity with H2O2 relative to abundant thiol peroxidases such as PRDX. Recent work has shown that following exposure to H2O2 in vitro, the sulfenic acid of the PRDX cysteine can form mixed disulphides with transcription factors associated with cell survival. This implicates PRDX as an ‘active’ redox relay in transmitting the oxidising equivalent of H2O2 to downstream proteins. Furthermore, under oxidative stress, PRDX can form stable oxidised dimers that can be secreted into the extracellular space, potentially acting as an extracellular ‘stress’ signal. There is extensive literature assessing non-specific markers of oxidative stress in response to exercise, however the PRDX catalytic cycle may offer a more robust approach for measuring changes in redox balance following exercise. This review discusses studies assessing PRDX-mediated cellular signalling and integrates the recent advances in redox biology with investigations that have examined the role of PRDX during exercise in humans and animals. Future studies should explore the role of PRDX as a key regulator of peroxide mediated-signal transduction during exercise in humans.

Peroxiredoxin (PRDX) is an abundant cellular antioxidant protein that may modulate hydrogen peroxide (H2O2) produced within skeletal muscle and other active cell types during exercise to elicit an adaptive biological response. Abbreviations: S----S, disulphide bond; PRDX, Peroxiredoxin; –SH, thiol group; SO2H, sulfinic acid; SO3H, sulphonic acid; catalytic (–S−) and resolving (–SH) cysteine thiols . Notes: Redox-sensitive protein targets (green).Figure optionsDownload as PowerPoint slide