The action of nitric oxide to enhance cell survival in chick cardiomyocytes is mediated through a cGMP and ERK1/2 pathway while p38 mitogen‐activated protein kinase‐dependent pathways do not alter cell death
Bibliographic record
Abstract
The objective of this study was to determine whether the dual action of nitric oxide (NO) on cardiomyocyte cell viability is mediated through p38 mitogen-activated protein kinase (MAPK)-induced cell death and extracellular signal-regulated kinase (ERK1/2)-mediated cell survival pathways, and whether either of these is mediated through a cGMP-protein kinase G (PKG) pathway. Cell viability of embryonic chick cardiomyocytes was assessed by the MTT assay, which is based on the ability of viable cells to reduce 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. The NO donor sodium nitroprusside (SNP) produced a significant (P < 0.01) concentration-dependent reduction in cell viability or increase in cell death. Sodium nitroprusside induced ERK1/2 phosphorylation, and the mitogen-activated protein kinase (MEK1/2) inhibitor PD 98059 significantly increased cell death. In contrast, SB202190, a relatively selective inhibitor of p38 MAPK, did not affect SNP-induced cell death. The cardioprotective effect of NO was prbably mediated in part via cGMP because 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a selective inhibitor of NO-sensitive guanylyl cyclase, produced a significant enhancement of SNP-induced cell death. In contrast, the PKG inhibitor KT5823 did not affect cell viability. In summary, these data suggest that NO, via stimulation of soluble guanylyl cyclase, activates MEK1/2 whose product, ERK1/2, protects against cell death. In contrast, SNP-induced p38 MAPK activation does not modulate NO-induced cardiomyocyte cell death. Not all cGMP targets affect NO-induced cell death, since the PKG pathway does not enhance or suppress NO-induced cardiomyocyte cell death. Enhancement of the ERK1/2 responses to NO may permit the beneficial effects of NO to predominate.
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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) | 0.001 | 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".