title: The basic chemistry of exercise-induced DNA oxidation: oxidative damage, redox signaling, and their interplay.
abstract: Acute exercise increases reactive oxygen and nitrogen species generation. This phenomenon is associated with two major outcomes: (1) redox signaling and (2) macromolecule damage. Mechanistic knowledge of how exercise-induced redox signaling and macromolecule damage are interlinked is limited. This review focuses on the interplay between exercise-induced redox signaling and DNA damage, using hydroxyl radical ((·)OH) and hydrogen peroxide (H2O2) as exemplars. It is postulated that the biological fate of H2O2 links the two processes and thus represents a bifurcation point between redox signaling and damage. Indeed, H2O2 can participate in two electron signaling reactions but its diffusion and chemical properties permit DNA oxidation following reaction with transition metals and (·)OH generation. It is also considered that the sensing of DNA oxidation by repair proteins constitutes a non-canonical redox signaling mechanism. Further layers of interaction are provided by the redox regulation of DNA repair proteins and their capacity to modulate intracellular H2O2 levels. Overall, exercise-induced redox signaling and DNA damage may be interlinked to a greater extent than was previously thought but this requires further investigation.
authors.affiliation: Division of Sport and Exercise Sciences, Abertay University Dundee, UK.
authors.forename: James N
authors.initials: JN
authors.lastname: Cobley
authors.affiliation: Exercise Physiology and Biochemistry Laboratory, School of Physical Education and Sport Sciences at Serres, Aristotle University of Thessaloniki Serres, Greece.
authors.forename: Nikos V
authors.initials: NV
authors.lastname: Margaritelis
authors.affiliation: Muscle Metabolism Research Group, Research Institute for Sport and Exercise Science, Liverpool John Moores University Liverpool, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Morton
authors.affiliation: Muscle Metabolism Research Group, Research Institute for Sport and Exercise Science, Liverpool John Moores University Liverpool, UK.
authors.forename: Graeme L
authors.initials: GL
authors.lastname: Close
authors.affiliation: Exercise Physiology and Biochemistry Laboratory, School of Physical Education and Sport Sciences at Serres, Aristotle University of Thessaloniki Serres, Greece.
authors.forename: Michalis G
authors.initials: MG
authors.lastname: Nikolaidis
authors.affiliation: Division of Sport and Exercise Sciences, Abertay University Dundee, UK.
authors.forename: John K
authors.initials: JK
authors.lastname: Malone
keywords: DNA damage; exercise; hydrogen peroxide; hydroxyl radical; mitochondrial DNA damage; redox signaling