The Role of Nrf2 in Muscle Phenotype and Mitochondrial Function
Bibliographic record
Abstract
Nuclear erythroid 2 p45-related factor 2 (Nrf2) has emerged as a master regulator of endogenous antioxidant enzyme expression through the transcriptional activation of the antioxidant response element (ARE) located within the promoter region of these genes. The Nrf2 signaling pathway is negatively regulated by Keap1. While it is well-established that the Keap1-Nrf2 pathway serves as a molecular switch that is highly responsive to the redox status of the cell, its expression and function within skeletal muscle remain to be elucidated. Thus, the purpose of our study was to examine the role of the Keap1-Nrf2 pathway in mediating changes in skeletal muscle phenotype using Nrf2 wild-type (WT) and knockout (KO) mice at 2.5 months of age. Despite a 29% greater body weight in the Nrf2 KO mice, there were no observed differences in TA mass between the two genotypes. Since Nrf2 has also been implicated in mitochondrial function, we subjected these mice to an endurance exercise capacity test. Interestingly, the Nrf2 KO mice exhibited a similar running capacity since their distance (1110m ±65) and time to exhaustion (62.6 min ±2.0) were the same as their WT counterparts. This may partially be explained by the lack of observed differences in mitochondrial content as measured by COX activity, or lactate production during exercise between the WT and KO mice. Similarly, PGC1α protein content did not differ between genotypes. These findings suggest that Nrf2 may be required for normal muscle growth, but that it is not essential to maintain mitochondrial content or endurance exercise performance in young animals. Supported by NSERC.
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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".