The basic chemistry of exercise-induced DNA oxidation: oxidative damage, redox signaling, and their interplay
Open accessAbstract
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.
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Exercise-induced disruptions in skeletal muscle homeostasis regulate exercise adaptations with repeated activation.
“It is now well recognized that exercise-induced disruptions in skeletal muscle homeostasis regulate exercise adaptations with repeated activation [148,149] (Figure 1)”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [149]
Repeated exercise bouts (training) induce disruption in skeletal muscle homeostasis that regulate training adaptations.
“It is accepted that repeated exercise bouts (i.e. training) induce disruption in skeletal muscle homeostasis that regulate training adaptations [62,63].”
From Sleep and Nutrition Interactions: Implications for Athletes (2019) · cites this paper as [62]
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García‐Giménez, J. L., Cánovas‐Cervera, I., & Pallardó, F. V. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.01.008 · Cited by 49 · see citing works
Targeted Antioxidants in Exercise-Induced Mitochondrial Oxidative Stress: Emphasis on DNA Damage
Williamson, J., & Davison, G. W. (2020) · Antioxidants · doi:10.3390/antiox9111142 · Cited by 41 · see citing works
Davison, G. W. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00249 · Cited by 38 · see citing works
Plant Aquaporins and Metalloids
Bienert, M. D., & Bienert, G. P. (2017) · Signaling and communication in plants · doi:10.1007/978-3-319-49395-4_14 · Cited by 35 · see citing works
Cobley, J. N., & Husi, H. (2020) · Antioxidants · doi:10.3390/antiox9040315 · Cited by 33 · see citing works
Self-citationMoreno‐Villanueva, M., Kramer, A., Hammes, T., Venegas-Carro, M., Thumm, P., Bürkle, A., & Grüber, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20122999 · Cited by 31 · see citing works
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Proteomic strategies to unravel age-related redox signalling defects in skeletal muscle
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Self-citationReversible Thiol Oxidation Inhibits the Mitochondrial ATP Synthase in Xenopus laevis Oocytes
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Pathophysiology of bronchoconstriction
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Oxidative stress in elite athletes training at moderate altitude and at sea level
León, J., Calderón‐Soto, C., Pérez‐Sánchez, M., Feriche, B., Iglesias, X., Chaverri, D., & Rodríguez, F. A. (2018) · European Journal of Sport Science · doi:10.1080/17461391.2018.1453550 · Cited by 20 · see citing works
Exploring the unmapped cysteine redox proteoform landscape
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Self-citationTuncay, A., Crabtree, D. R., Muggeridge, D. J., Husi, H., & Cobley, J. N. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.05.006 · Cited by 17 · see citing works
Self-citationHow exercise induces oxidative eustress
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Self-citationAshraf, W., Ahmad, T., Almalki, N. A. R., Krifa, M., Zaayter, L., Pizzi, A., Muller, C. D., Hamiche, A., Mély, Y., Bronner, C., et al. (2021) · Food & Function · doi:10.1039/d1fo01484f · Cited by 13 · see citing works
Ten “Cheat Codes” for Measuring Oxidative Stress in Humans
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Self-citationSleep and Nutrition in Athletes
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Exercise-induced oxidatively damaged DNA in humans: evaluation in plasma or urine?
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Marked differences in redox status of professional soccer players depending on training types
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Proteoforms as the true units of physiological function
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Self-citationAgronomics Management for Arsenic Stress Mitigation
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Impact of exercise-induced DNA damage repair on age-related muscle weakness and sarcopenia
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Th17 cells require the DNA repair sensor XPC to control oxidative DNA damagePreprint
Leite, J. A., Bos, N. N., Menezes-Silva, L., Martins, E., Leandro, G. D. S., da Silva, P., Ranfley, H., Oliveira, S. D. P., Ferreira, C. P., Neto, J. A. D. O. N., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.13.612834
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- Authors
- Cobley, J. N., Margaritelis, N. V., Morton, J. P., Close, G. L., Nikolaidis, M. G., & Malone, J. K.
- Affiliations
- Abertay University (GB)
- Aristotle University of Thessaloniki (GR)
- Liverpool John Moores University (GB)
- Corresponding author
- Cobley, James N.
- Venue
- Frontiers in Physiology
- Publisher
- Frontiers Media SA
- Published
- 2015-06-17
- Volume
- 6
- Pages
- 182-182
- ISSN
- 1664-042X (ISSN-L)
- PMC
- PMC4469819
- OpenAlex
- W1588923203
- Cited by
- 43
- References
- 87
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 9 · 2019: 6 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 3
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Physiology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Abertay Research Portal (Abertay University) (acceptedVersion, cc-by)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- University of Otago
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- oxidative DNA damage, redox signaling, hydrogen peroxide, hydroxyl radicals, reactive oxygen species, reactive nitrogen species, transition metal catalysis, DNA repair proteins, exercise physiology
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