Peroxiredoxin 2 is required for the redox mediated adaptation to exercise

Abstract

Exercise generates a site-specific increase in Reactive Oxygen Species (ROS) within muscle required for a beneficial adaptive response by activation of specific signalling pathways. Here, we demonstrate that Peroxiredoxin 2 (Prdx2), an abundant cytoplasmic 2-Cys peroxiredoxin, is required for the adaptive beneficial hormesis response to H2O2. A short bolus addition of H2O2 increases mitochondrial capacity and improves myogenesis of cultured myoblasts, this beneficial adaptive response was suppressed in myoblasts with decreased expression of cytoplasmic Prdxs. A swimming exercise protocol in C. elegans increased mitochondrial content, fitness, survival and longevity in wild type (N2) worms. In contrast, prdx-2 mutant worms had decreased fitness, disrupted mitochondria, reduced survival and lifespan following exercise. Global proteomics following exercise identified distinct changes in the proteome of N2 and prdx-2 mutants. Furthermore, a redox proteomic approach to quantify reversible oxidation of individual Cysteine residues revealed a relatively more oxidised redox state following exercise in the prdx-2 mutants. Our results demonstrate that conserved cytoplasmic 2-Cys Peroxiredoxins are required for the beneficial adaptive response to a physiological stress.

Muscle of obese insulin-resistant humans exhibits losses in proteostasis and attenuated proteome dynamics that are improved by exercise training

“…PARK7 is a redox-sensitive chaperone that may reverse methylglyoxal and glyoxal-glycated protein modifications (Richarme et al, 2015) that can be elevated in the muscle of obese individuals with type 2 diabetes (Mey et al, 2018). PRDX enzymes are the primary scavengers of cellular H2O2 and may underpin the hormesis response of muscle to exercise-induced oxidative stress (Xia et al, 2023). Our findings (Figure 4E and F) add to reports that PRDX2 and PRDX6 are more abundant in the skeletal muscle of type 2 diabetic patients (Brinkmann et al, 2012), and that PRDX5 in more abundant in myoblasts derived from muscle biopsies of type 2 diabetic patients (Al-khalili et al, 2013).…”