Short Communication: Antiretroviral Protease Inhibitors Prevent L6 Muscle Cell Fusion by Reducing Calpain Activity
Bibliographic record
Abstract
The antiretroviral protease inhibitors indinavir (IDV) and ritonavir (RTV) are used in highly active antiretroviral therapies (HAART). Side effects from long-term HAART therapy include loss of muscle mass. Myoblasts when cultured in media low in growth factors withdraw from the cell cycle, express muscle-specific differentiation inducers and proteins, and fuse to form myotubes. The neutral protease, calpain, is required for myotube formation and RTV decreased calpain activity in vitro. We found lower calpain activity, but not protein, in homogenates of RTV-treated L6 cells than in control cultures. Importantly, L6 and C2C12 myoblasts did not form myotubes when cultured with 10 or 20 microM IDV or RTV. Control and drug-related L6 myoblasts showed identical decreases in proliferating cell nuclear antigens expression indicating proliferation arrest. Similarly, muscle differentiation inducers MyoD and myogenin and their downstream target, myosin heavy chain, were expressed at similar levels in control and drug-treated cells. Thus, whereas muscle differentiation was unaffected by protease inhibitors, calpain activity was reduced and myotube formation prevented. We conclude that RTV and IDV reduced myotube formation by reducing calpain activity. Our data suggest that protease inhibitors included in HAART might be directly involved in muscle wasting by reducing muscle remodeling.
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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 | 0.001 | 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 | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".