Inhibition of phospholipase C decreased cardiac COX‐2 expression and attenuated myocardial dysfunction during endotoxemia
Bibliographic record
Abstract
Lipopolysaccharide (LPS) up‐regulates COX‐2 expression in cardiomyocytes and inhibition of COX‐2 attenuates myocardial dysfunction in endotoxemia. The mechanism of LPS‐induced COX‐2 expression in cardiomyocytes has not been fully understood. Our previous study has demonstrated that NADH oxidase‐mediated MAPK signaling contributes to COX‐2 expression in LPS‐stimulated cardiomyocytes. The purpose of this study was to investigate the role of phospholipase C (PLC) in cardiac COX‐2 expression during endotoxemia. Wild‐type and PLC?1+/− adult mice were treated with LPS (4 mg/kg, i.p.) in the presence of U73122, a specific inhibitor of PLC or U74133, an analog control for U73122, or vehicle for 2 hours. COX‐2 mRNA expression was analyzed by real‐time Reverse Transcription Polymerase Chain Reaction (RT‐PCR) and phosphorylation of ERK1/2 was determined by Western blot in the myocardial tissues. U73122 treatment or deficiency of PLC?1 decreased cardiac COX‐2 mRNA by 60% and 40%, respectively, suggesting an important role of PLC?1. The contribution of PLC to COX‐2 expression was likely mediated through an attenuation of ERK1/2 activation as U73122 significantly decreased phosphorylation of ERK1/2 in LPS‐stimulated hearts. In addition, both U73122 and deficiency of PLC?1 significantly attenuated LPS‐induced myocardial depression. In conclusion, our data demonstrated that PLC?1 plays important role in cardiac COX‐2 expression and myocardial dysfunction during endotoxemia.
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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 | 0.000 |
| 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 | 0.001 |
| 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".