Norepinephrine inhibits cell cycle re‐entry of neonatal rat ventricular cardiomyocytes characterized by the absence of de novo nestin expression
Bibliographic record
Abstract
Abstract The p38α/β MAPK inhibitor SB203580 in the presence of a phorbol ester (protein kinase C activator) induced cell cycle re‐entry of two subpopulations of neonatal rat ventricular cardiomyocytes (NNVMs) distinguished by the absence or de novo nestin expression. Recent studies have reported that the β‐adrenergic receptor inhibited the cell cycle re‐entry of ventricular cardiomyocytes. The present study tested the hypothesis that sympathetic recruitment of p38α/β MAPK signaling suppressed cell cycle re‐entry of one or both subpopulations of 1‐day‐old NNVMs. Norepinephrine (NE; 1 μM) or Isoproterenol (ISO; 1 μM) treatment of NNVMs for 24 h significantly attenuated 5‐bromo‐2′‐deoxyuridine incorporation, and NE increased p38α MAPK phosphorylation. SB203580 (10 μM) treatment of NE/ISO‐stimulated NNVMs selectively re‐established the cell cycle re‐entry of the subpopulation distinguished by the absence of de novo nestin expression. Phorbol 12,13‐dibutyrate (PDBu; 100 nM) treatment attenuated 5‐bromo‐2′‐deoxyuridine incorporation, and SB203580 treatment predominantly initiated re‐entry into the cell cycle of the NNVM subpopulation characterized by de novo nestin expression. siRNA‐mediated PKC‐α protein downregulation in NNVMs selectively suppressed PDBu/SB203580‐mediated de novo nestin and subsequent cell cycle re‐entry. Thus, sympathetic stimuli acting via the β 1/2 ‐adrenergic receptor selectively inhibited the cell cycle re‐entry of the nestin (−) ‐NNVM subpopulation via recruitment of p38α/β MAPK.
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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".