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2-Cys Peroxiredoxin oxidation in response to Hydrogen Peroxide and contractile activity in skeletal muscle: A novel insight into exercise-induced redox signalling?

Stretton, C, Pugh, JN, McDonagh, B, McArdle, A, Close, GL and Jackson, MJ (2020) 2-Cys Peroxiredoxin oxidation in response to Hydrogen Peroxide and contractile activity in skeletal muscle: A novel insight into exercise-induced redox signalling? Free Radical Biology and Medicine. ISSN 0891-5849

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Open Access URL: https://doi.org/10.1016/j.freeradbiomed.2020.06.02... (Published version)

Abstract

Skeletal muscle generates superoxide during contractions which is rapidly converted to H2O2. This molecule has been proposed to activate signalling pathways and transcription factors that regulate key adaptive responses to exercise but the concentration of H2O2 required to oxidise and activate key signalling proteins in vitro is much higher than the intracellular concentration in muscle fibers following exercise. We hypothesised that Peroxiredoxins (Prx), which reacts with H2O2 at the low intracellular concentrations found in muscle, would be rapidly oxidised in contracting muscle and hence potentially transmit oxidising equivalents to downstream signalling proteins as a method for their oxidation and activation. The aim of this study was to characterise the effects of muscle contractile activity on the oxidation of Prx1, 2 and 3 and determine if these were affected by aging. Prx1, 2 and 3 were all rapidly and reversibly oxidised following treatment with low micromolar concentrations of H2O2 in C2C12 myotubes and also in isolated mature flexor digitalis brevis fibers from adult mice following a protocol of repeated isometric contractions. Significant oxidation of Prx2 was seen within 1 minute (i.e. after 12 contractions), whereas significant oxidation was seen after 2 minutes for Prx1 and 3. In muscle fibers from old mice, Prx2 oxidation was significantly attenuated following contractile activity. Thus we show for the first time that Prx are rapidly and reversibly oxidised in response to contractile activity in skeletal muscle and hypothesise that these proteins act as effectors of muscle redox signalling pathways which are key to adaptations to exercise that are attenuated during aging.

Item Type: Article
Uncontrolled Keywords: 0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 1101 Medical Biochemistry and Metabolomics
Subjects: R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions: Sport & Exercise Sciences
Publisher: Elsevier
Related URLs:
Date Deposited: 21 Aug 2020 12:52
Last Modified: 21 Aug 2020 12:52
DOI or Identification number: 10.1016/j.freeradbiomed.2020.06.020
URI: https://researchonline.ljmu.ac.uk/id/eprint/13531

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