Antioxidant mito-TEMPO prevents the increase in tropomyosin oxidation and mitochondrial calcium accumulation under 7-day rat hindlimb suspension
Abstract
After the first day of muscle disuse (unloading) mitochondria-derived ROS accumulate in the postural-tonic soleus muscle. It is known that excess of ROS can lead to the accumulation of intramitochondrial calcium and overload of mitochondria with calcium, can negatively affect mitochondrial function and fatigue resistance of soleus muscle. We assumed that the use of mitochondrial ROS scavenger mito-TEMPO will be able to prevent the unloading-induced disruption of mitochondrial functions and will help maintain soleus muscle fatigue resistance. To test this hypothesis, male rats were divided into 3 groups (n = 16 in each): vivarium control with placebo (C), 7-day hindlimb suspension with placebo (7HS) and 7-day hindlimb suspension with intraperitoneal administration of the mimetic superoxide dismutase mito-TEMPO at a dose of 1 mg/kg (7HSM). In the 7HS group, increased fatigue of the soleus muscle was found in the ex vivo test, accompanied with increased activity of ETC complex I and "leak" respiration, as well as a twofold increased content of oxidized tropomyosin (a marker of ROS level in tissues) and increase in intramitochondrial calcium compared to C. In 7HSM, the activity of ETC complex I and "leak" respiration had no significant differences from the control group, and the increase in intramitochondrial calcium and the content of oxidized tropomyosin was partially prevented, however, muscle fatigue was also significantly higher than in the control group. Thus, mitochondrial ROS under 7-day muscle unloading contribute to the accumulation of intramitochondrial calcium and oxidation of tropomyosin, but do not have a significant effect on soleus muscle function.
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Mito-TEMPO prevents unloading-induced mitochondrial dysfunction and preserves fatigue resistance in rat soleus muscle.
“treatment with the mitochondrial ROS scavenger mito-TEMPO prevents unloading-induced mitochondrial dysfunction and helps preserve fatigue resistance in the soleus muscle in rats [33].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [33]
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- Authors
- Sidorenko, D. A., Galkin, G. V., Bokov, R. O., Tyrina, E. A., Vilchinskaya, N. A., Lvova, I. D., Tyganov, S. A., Shenkman, B. S., & Sharlo, K. A.
- Affiliations
- Institute of Biomedical Problems (RU)
- Corresponding author
- Sharlo, Kristina A.
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2024-11
- Volume
- 224
- Pages
- 822-830
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W4403374750
- Cited by
- 7
- References
- 38
- Citations by year
- 2026: 2 · 2025: 5
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Russian Science Foundation (23-75-10048)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Spaceflight effects on biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- MitoTEMPO, mitochondrial reactive oxygen species, muscle unloading, hindlimb unloading, soleus muscle, muscle fatigue, mitochondrial calcium, mitochondrial calcium accumulation, complex I activity, leak respiration, antioxidant therapy
- MeSH terms
- Animals, Antioxidants, Calcium, Male, Mitochondria, Mitochondria, Muscle, Organophosphorus Compounds, Oxidation-Reduction, Piperidines, Spin Labels, Tropomyosin, Rats, Wistar, Reactive Oxygen Species, Muscle, Skeletal, Muscle Fatigue, Hindlimb Suspension, Rats
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