Exercise decreases PP2A-specific reversible thiol oxidation in human erythrocytes: Implications for redox biomarkers

David J Muggeridge, Daniel R Crabtree, Ahmet Tuncay, Ian L Megson, Gareth Davison, James N Cobley

Research output: Contribution to journalArticlepeer-review

Abstract

New readily accessible systemic redox biomarkers are needed to understand the biological roles reactive oxygen species (ROS) play in humans because overtly flawed, technically fraught, and unspecific assays severely hamper translational progress. The antibody-linked oxi-state assay (ALISA) makes it possible to develop valid ROS-sensitive target-specific protein thiol redox state biomarkers in a readily accessible microplate format. Here, we used a maximal exercise bout to disrupt redox homeostasis in a physiologically meaningful way to determine whether the catalytic core of the serine/threonine protein phosphatase PP2A is a candidate systemic redox biomarker in human erythrocytes. We reasoned that: constitutive oxidative stress (e.g., haemoglobin autoxidation) would sensitise erythrocytes to disrupted ion homeostasis as manifested by increased oxidation of the ion regulatory phosphatase PP2A. Unexpectedly, an acute bout of maximal exercise lasting ~16 min decreased PP2A-specific reversible thiol oxidation (redox ratio, rest: 0.46; exercise: 0.33) without changing PP2A content (rest: 193 pg/ml; exercise: 191 pg/ml). The need for only 3–4 μl of sample to perform ALISA means PP2A-specific reversible thiol oxidation is a capillary—fingertip blood—compatible candidate redox biomarker. Consistent with biologically meaningful redox regulation, thiol reductant-inducible PP2A activity was significantly greater (+10%) at rest compared to exercise. We establish a route to developing new readily measurable protein thiol redox biomarkers for understanding the biological roles ROS play in humans.

Original languageEnglish
Pages (from-to)73-78
Number of pages6
JournalFree Radical Biology and Medicine
Volume182
Early online date22 Feb 2022
DOIs
Publication statusPublished - 31 Mar 2022

Bibliographical note

Funding Information:
We acknowledge the participants who made the present work possible and thank the EU INTERREG VA programme (D.C.) and Highlands and Islands Enterprise ( HMS 9533763 , J.N.C and D.C.) for funding the present work. The graphical abstract, Fig. 1 , and Fig. 3 D were created using BioRender ( www.Biorender.com ) and exported with the appropriate publication license.

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

  • ALISA
  • Exercise
  • Oxidative stress
  • Redox signalling
  • Biomarker
  • PP2A
  • Protein thiol
  • Human

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