Oxidized DNA repair enzymes protect skeletal muscle from oxidative stress during differentiation and contractile activity
Bibliographic record
Abstract
Mitochondria play a central role in maintaining skeletal muscle homeostasis. Beyond energy production, mitochondria serve as the primary source of reactive oxygen species (ROS) during muscle fiber contraction. An imbalance between ROS production and clearance leads to oxidative stress, a phenomenon previously observed during myoblast differentiation and muscle fiber contraction. As the mitochondrial electron transport chain (ETC) produces a significant amount of ROS, mitochondrial DNA (mtDNA), due to its proximity, is particularly susceptible to damage from these ROS. Oxidized mtDNA released into the cytosol has emerged as one of the key mitochondrial damage-associated molecular patterns (mtDAMPs), capable of activating inflammatory signaling pathways involved in myofibril regeneration. However, excessive release of mtDAMPs can overstimulate inflammatory signaling, resulting in maladaptive responses and impaired muscle recovery. This necessitates the importance of the removal of mtDAMPs to maintain muscle health. Thus, the objective of this study is to decipher if exercise can modulate the levels of oxidized mtDNA repair enzymes, thereby mitigating the level and release of oxidized mtDNA. To address this, we investigated the expression of key antioxidant enzymes and oxidized DNA repair enzymes, such as OGG1 and YB1, during skeletal muscle differentiation and acute muscle fiber contraction using C2C12 myoblasts and their differentiated myotubes. Our findings revealed a more than 2-fold increase in both mRNA and protein levels of YB1 and OGG1 in differentiated myotubes compared to myoblasts, accompanied by a concurrent 4-fold decrease in oxidized mtDNA levels. Western blot analyses further demonstrated the progressive mitochondrial translocation of OGG1 protein from mitochondria to cytosol as differentiation proceeds. Additionally, after 3 hours of acute contractile activity, protein levels of both YB1 and OGG1 were elevated by 2-fold and 3-fold respectively, despite no detectable changes in their mRNA levels. Collectively, these initial findings suggest that both myoblasts and myotubes adapt oxidized mtDNA repair mechanisms as a protective measure against oxidative stress during differentiation and acute contractile activity. Supported by NSERC Canada This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".