Oxidative stress response triggered by the lipid drug edelfosine indicates lipid peroxidation mediates its cytotoxic effect in yeast
Bibliographic record
Abstract
Edelfosine (1‐O‐octadecyl‐2‐O‐methyl‐rac‐glycero‐3‐phosphocholine) is the prototype of a family of lipid drugs that interferes with cellular membrane function and selectively induces apoptosis in tumor cells. It has been difficult to further optimize its efficacy as its cellular target(s) has yet to be elucidated. Previously, we have validated S. cerevisiae as model system to study the biochemistry and mode of action of Edelfosine. In this study, we have found that microM concentrations of the antioxidant Vitamin E (alpha‐tocopherol) protected yeast cells from Edelfosine cytotoxicity. We have assessed the possibility of Vitamin E correcting the membrane curvature introduced by Edelfosine. Cells were then challenged with a methylated Vit E that has lost its antioxidant properties but could still be inserted into membranes. This compound could not protect cells from Edelfosine, indicating lipid peroxidation mediates its cytotoxic effect. Furthermore, a genetic approach using strains lacking genes known to protect yeast from oxidative stress identified a small set of mutants lacking phospholipid hydroperoxide glutathione peroxidases (GPX1, GPX2 and GPX3) and the two master transcription factors, YAP1 and SKN7, required for oxidative stress tolerance, as hypersensitive to the drug. Altogether these results strongly support lipid peroxidation mediates Edelfosine effect.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".