GSK‐3b inactivation in preventing the myocardium from I/R‐induced injury: Role of eNOS‐derived NO
Bibliographic record
Abstract
Inhibition of glycogen synthase kinase (GSK)‐3b has been shown to reduce myocardial cell death following ischemia/reperfusion (I/R). However, the downstream targets of GSK‐3b inactivation are not fully understood. The present study was to investigate the role of endothelial nitric oxide synthase (eNOS) as a downstream target of GSK‐3b inactivation in preventing the myocardium from I/R‐induced injury. Isolated neonatal mouse cardiomyocytes were exposed to anoxia/reoxygenation (A/R; the in vitro counterpart to I/R). Nitric oxide (NO) production and caspase‐3 activity were measured after A/R. Inhibition of GSK‐3b with lithium or SB216763 increased NO production by 3‐fold and reduced A/R‐induced caspase‐3 activation in cardiomyocytes. The effects of lithium or SB216763 on NO production and caspase‐3 activation were absent in eNOS‐/‐ cardiomyocytes. Additionally, a NOS inhibitor, L‐NAME blocked lithium or SB216763‐induced protection after A/R. To investigate the functional significance of GSK‐3b inactivation, isolated mouse hearts were perfused using a Langendorff system. Perfused hearts were subjected to 30 minutes of global ischemia followed by 1 hour of reperfusion. Phosphorylation of eNOS, cardiac apoptosis and myocardial function were assessed after I/R. Lithium treatment during reperfusion increased phosphorylation of eNOS by 4‐fold in the myocardium, reduced cardiac apoptosis and restored myocardial function after global I/R. These protective effects of lithium were not seen in eNOS−/ − hearts. In conclusion, the present studyidentified eNOS‐derived NO as a novel downstream target of GSK‐3beta inactivation in preventing the myocardium from I/R‐induced injury.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.001 |
| 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".