Effect of denervation on mitochondrial function and the expression of apoptotic related proteins
Bibliographic record
Abstract
Chronic skeletal muscle disuse results in a loss of muscle mass which is partly attributable to apoptosis. This study was designed to evaluate the relationship between changes in mitochondrial function and apoptosis in chronic denervation (7, 14, 21 days) of rat tibialis anterior (TA) muscle. Denervation decreased state 3 (ADP‐stimulated) respiration in subsarcolemmal (SS) mitochondria by 37 – 45 % between 7 and 21 days, whereas no changes were evident in intermyofibrillar (IMF) mitochondria. Conversely, state 4 respiration increased by 68% in IMF mitochondria with 14 days of denervation, while it remained unchanged in the SS mitochondria. This was accompanied by a 2.3‐fold increase in UCP3 expression at 14 days of denervation. The expression of the anti‐oxidant enzyme MnSOD declined 60–70% in SS and IMF mitochondria, whereas the production of reactive oxygen species (ROS) was elevated 5–10‐fold in the SS mitochondrial subfraction. In addition, there was a 76% increase in the expression of the pro‐apoptotic protein p53 at 14 days of denervation. This was matched by an increase in DNA fragmentation, assessed using TUNEL staining. An elevation in apoptotic nuclei was evident as early as 7 days, which remained similarly elevated at 14 and 21 days. Thus chronic muscle denervation: 1) induces impairments in mitochondrial function, leading to increased ROS production; and 2) increases the expression of pro‐apoptotic proteins while reducing the protective effects of anti‐oxidant enzymes. These data suggest that mitochondrially mediated apoptosis contributes to the muscle atrophy which is observed during muscle disuse.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".