Pyruvate reduces DNA damage during hypoxia and after reoxygenation in hepatocellular carcinoma cells
Bibliographic record
Abstract
Pyruvate is located at a crucial crossroad of cellular metabolism between the aerobic and anaerobic pathways. Modulation of the fate of pyruvate, in one direction or another, can be important for adaptative response to hypoxia followed by reoxygenation. This could alter functioning of the antioxidant system and have protective effects against DNA damage induced by such stress. Transient hypoxia and alterations of pyruvate metabolism are observed in tumors. This could be advantageous for cancer cells in such stressful conditions. However, the effect of pyruvate in tumor cells is poorly documented during hypoxia/reoxygenation. In this study, we showed that cells had a greater need for pyruvate during hypoxia. Pyruvate decreased the number of DNA breaks, and might favor DNA repair. We demonstrated that pyruvate was a precursor for the biosynthesis of glutathione through oxidative metabolism in HepG2 cells. Therefore, glutathione decreased during hypoxia, but was restored after reoxygenation. Pyruvate had beneficial effects on glutathione depletion and DNA breaks induced after reoxygenation. Our results provide more evidence that the alpha-keto acid promotes the adaptive response to hypoxia followed by reoxygenation. Pyruvate might thus help to protect cancer cells under such stressful conditions, which might be harmful for patients with tumors.
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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".