The effect of sodium nitroprusside on survival and stress signaling in PC12 rat phaeochromocytoma cells expressing a dominant negative RasH mutant protein
Bibliographic record
Abstract
Toxic concentrations of the second messenger nitric oxide cause cellular stress leading to cell death. Ras proteins, possible targets of nitric oxide-induced nitrosylation, may act as mediators in nitrosative stress. To analyze the possible involvement of Ras proteins in nitric oxide cytotoxicity, a PC12 rat phaeochromocytoma cell line expressing a dominant negative Ras mutant protein was used in this study. Cytotoxic concentrations of the nitric oxide donor sodium nitroprusside activated several proapoptotic mechanisms, including stimulation of the stress kinase pathways mediated by c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), inhibition of the translation initiation factor eIF2α, induction and phosphorylation of the p53 protein, and inhibited Akt-mediated antiapoptotic signaling, independent of Ras function. Simultaneously, Ras-dependent stimulation of the prosurvival ERK pathway was also observed, followed by an increased activation of the caspase-9/caspase-3 cascade in cells with impaired Ras function. It is concluded that nitric oxide stimulation of multiple signaling pathways contributes to the cell death program, whereas concomitant activation of the Ras/ERK pathway provides a certain degree of protection.
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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".