Skeletal Muscle Contractions Induce Acute Changes in Cytosolic Superoxide, but Slower Responses in Mitochondrial Superoxide and Cellular Hydrogen Peroxide
Open accessAbstract
Skeletal muscle generation of reactive oxygen species (ROS) is increased following contractile activity and these species interact with multiple signaling pathways to mediate adaptations to contractions. The sources and time course of the increase in ROS during contractions remain undefined. Confocal microscopy with specific fluorescent probes was used to compare the activities of superoxide in mitochondria and cytosol and the hydrogen peroxide content of the cytosol in isolated single mature skeletal muscle (flexor digitorum brevis) fibers prior to, during, and after electrically stimulated contractions. Superoxide in mitochondria and cytoplasm were assessed using MitoSox red and dihydroethidium (DHE) respectively. The product of superoxide with DHE, 2-hydroxyethidium (2-HE) was acutely increased in the fiber cytosol by contractions, whereas hydroxy-MitoSox showed a slow cumulative increase. Inhibition of nitric oxide synthases increased the contraction-induced formation of hydroxy-MitoSox only with no effect on 2-HE formation. These data indicate that the acute increases in cytosolic superoxide induced by contractions are not derived from mitochondria. Data also indicate that, in muscle mitochondria, nitric oxide (NO) reduces the availability of superoxide, but no effect of NO on cytosolic superoxide availability was detected. To determine the relationship of changes in superoxide to hydrogen peroxide, an alternative specific approach was used where fibers were transduced using an adeno-associated viral vector to express the hydrogen peroxide probe, HyPer within the cytoplasmic compartment. HyPer fluorescence was significantly increased in fibers following contractions, but surprisingly followed a relatively slow time course that did not appear directly related to cytosolic superoxide. These data demonstrate for the first time temporal and site specific differences in specific ROS that occur in skeletal muscle fibers during and after contractile activity.
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Mitochondria are not responsible for ROS generation during exercise.
“However, mitochondria are not responsible for ROS generation during exercise (20–22).”
From Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance (2021) · cites this paper as [22]
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- Authors
- Pearson, T., Kabayo, T., Ng, R., Chamberlain, J., McArdle, A., & Jackson, M. J.
- Affiliations
- University of Liverpool (GB)
- University of Washington (US)
- Corresponding author
- Jackson, Malcolm J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-05-29
- Volume
- 9
- Issue
- 5
- Pages
- e96378
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4038480
- OpenAlex
- W2132943675
- Cited by
- 107
- References
- 38
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 8 · 2023: 7 · 2022: 5 · 2021: 6 · 2020: 13 · 2019: 12 · 2018: 8 · 2017: 5 · 2016: 21 · 2015: 8 · 2014: 1
- FWCI
- 11.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (5f32ar057651-02)
- Medical Research Council (MR/K006312/1, G1002120)
- National Institute on Aging (AG033610, R01AG033610)
- National Institute of Neurological Disorders and Stroke
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (1F32AR057651, F32 AR057651, R01AR044533)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- skeletal muscle contraction, reactive oxygen species, mitochondrial superoxide, hydrogen peroxide, nitric oxide, nitric oxide synthase, MitoSOX Red, dihydroethidium, adeno-associated virus vectors
- MeSH terms
- Animals, Hydrogen Peroxide, Male, Mitochondria, Muscle Contraction, Superoxides, Reactive Oxygen Species, Muscle, Skeletal, Muscle Fibers, Skeletal, Intracellular Space, Mice
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