RhoA links PI3K/Akt/mTOR signaling to p38 MAPK/GATA‐4 activation in leptin–induced cardiomyocyte hypertrophy
Bibliographic record
Abstract
Obesity is associated with increased leptin production which may contribute to cardiac hypertrophy. However, the mechanism of leptin‐induced cardiac hypertrophy remains incompletely understood. The Rho family and mTOR have recently emerged as important regulators of cell growth. In this study we explored the roles of phosphatidylinositol 3‐kinase (PI3K), mTOR and the Rho family in the regulation of actin polymerization in leptin‐induced hypertrophy in cultured neonatal rat cardiomyocytes treated with 3.1 nM leptin. Leptin treatment resulted in activation of RhoA and Rac1 (by 330% and 160%, respectively; P<0.05) but not cdc42, 5 min after treatment, as determined by Western blotting. The hypertrophic effect of leptin was associated with an increase in phosphorylation of p70 S6K by 110% (P<0.05). The specific mTOR inhibitor, rapamycin (10 nM) attenuated leptin‐induced RhoA and Rac1 activation. Furthermore, the decrease in the G/F actin ratio, a measure of actin polymerization, was blunted by rapamycin. Leptin produced activation of the transcriptional factor GATA‐4 which was attenuated by the RhoA inhibitor C3, the p38 MAPK inhibitor SB203580 (10 µM) or rapamycin. Our results demonstrate that leptin‐induced cardiomyocyte hypertrophy is associated with GATA‐4 activation which is dependent on RhoA, PI3K/mTOR/p70 S6K and p38 MAPK pathways. Supported by the Canadian Institutes of Health Research.
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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 | 0.001 |
| 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".