Essential role of Rho/ROCK-dependent processes and actin dynamics in mediating leptin-induced hypertrophy in rat neonatal ventricular myocytes
Bibliographic record
Abstract
BACKGROUND: Obesity is associated with increased leptin production, which may contribute to cardiac hypertrophy. Although leptin has been shown to produce cardiomyocyte hypertrophy, its mechanism of action is far from clear. Rho proteins have been suggested as major contributors to cardiac hypertrophy, although their potential role in mediating the effect of leptin has not been studied. METHODS: We determined the role of Rho and Rho-associated kinase (ROCK) as mediators of leptin-induced cell hypertrophy in cultured neonatal rat ventricular myocytes. RESULTS: Leptin (3.1 nmol/L) significantly increased cell surface area by 32+/-5% and leucine incorporation by 43 +/- 7%. These effects were associated with significant activation of RhoA to 450 +/- 40% of pre-leptin levels that was attenuated by pretreatment with an anti-leptin receptor (anti-OBR) antibody (166 ng/mL) to 120 +/- 20% of control values. Both the RhoA inhibitor C3 exoenzyme and ROCK inhibitor Y-27632 potently attenuated leptin-induced increased cell surface area and leucine incorporation. The hypertrophic effect of leptin was associated with an increase in phosphorylation of the actin binding protein cofilin to 290 +/- 20% of control values. In addition, the increase in polymerization of actin, as reflected by a decrease in the G/F-actin ratio, was significantly inhibited by both the anti-OBR antibody and Y-27632. Leptin-induced hypertrophy was also attenuated by disruption of actin filaments with 50 nmol/L latrunculin B. RhoA pathway inhibitors and latrunculin B also both attenuated leptin-induced ERK1/2 and p38 activation. CONCLUSION: Our results indicate that the activation of Rho and actin dynamics play a pivotal role in leptin signaling leading to the development of cardiomyocyte hypertrophy.
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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) | 0.000 | 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 | 0.000 |
| 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".