Leptin-induced cardiomyocyte hypertrophy involves selective caveolae and RhoA/ROCK-dependent p38 MAPK translocation to nuclei
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Bibliographic record
Abstract
AIMS: Leptin-induced cardiomyocyte hypertrophy is dependent on both RhoA and p38 mitogen-activated protein kinase (p38 MAPK) activation. The present study investigated the role of lipid raft/caveolae in these responses and assessed the nature of p38 MAPK activation in mediating leptin-induced hypertrophy. METHODS AND RESULTS: Studies were carried out using cultured neonatal rat ventricular myocytes. Pharmacological, molecular, microscopy, and confocal imaging techniques were used to assess the role of caveolae in leptin-induced hypertrophy and to study the underlying cellular mechanisms. Leptin (3.1 nmol/L) treatment for 24 h significantly increased caveolae number two-fold and increased expression of caveolin-3 to 278 +/- 14% of control values. These effects were associated with increased cell surface area by 29 +/- 5% and leucine incorporation by 40 +/- 6%. The hypertrophic effect of leptin was associated with significant activation of RhoA (422 +/- 26%) and a decrease in the G-actin-to-F-actin ratio from 3.1 +/- 0.2 to 0.9 +/- 0.1. Caveolae disruption with methyl-beta-cyclodextrin (MbetaCD) potently attenuated leptin-induced cell hypertrophy and the associated signalling. RhoA was detected in caveolae fraction of a sucrose gradient after treatment with leptin for 5 min, indicating subcellular translocation of RhoA: this effect was inhibited by MbetaCD, the RhoA inhibitor C3 exoenzyme, and by disruption of actin filaments with latrunculin B. Furthermore, leptin-induced hypertrophy was associated with p38 MAPK but not with extracellular signal-regulated kinase (ERK1/2) translocation to nuclei, which was inhibited by MbetaCD, C3 exoenzyme, and the Rho kinase inhibitor Y-27632. CONCLUSION: Our results indicate that p38 import into nuclei represents a key mechanism for leptin-induced hypertrophy acting through lipid raft/caveolae and a RhoA-dependent pathway.
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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 | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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 it