Autophagy is required and protects against apoptosis during myoblast differentiation
Bibliographic record
Abstract
Several degradative systems assist in formation of multinucleated terminally differentiated myotubes. However, the role of autophagy in this process has not been examined. GFP-LC3B (light chain 3 beta) puncta, LC3B-II protein and LysoTracker fluorescence increased during C2C12 cell differentiation. Importantly, accumulation of LC3B-II protein occurred in CQ (chloroquine)-treated cells throughout differentiation. Furthermore, BECN1 (beclin 1), ATG7 (autophagy-related 7) and ATG12-5 protein increased, whereas SQSTM1/p62 (sequestosome 1) protein was rapidly reduced during differentiation. A transient decrease in BECN1-BCL2 association was observed from day 0.5 to 2 of differentiation. Chemical inhibition of JNK (c-Jun N-terminal kinase) during differentiation reduced LC3B-II protein and GFP-LC3B puncta and maintained BECN1-BCL2 association. Inhibition of autophagy by 3MA (3-methyladenine) or shRNA against Atg7 (shAtg7) resulted in lower myosin heavy chain expression, as well as impaired myoblast fusion and differentiation. Interestingly, 3MA treatment during differentiation increased transient CASP3 (caspase 3) activation, DNA fragmentation and the percentage of apoptotic nuclei. Similarly, shAtg7 cells had increased DNA fragmentation during differentiation compared with the controls. Collectively, these data demonstrate that autophagy increases and is required during myoblast differentiation. Moreover, autophagy protects differentiating myoblasts from apoptotic cell death.
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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".