The role of AMP-activate protein kinase (AMPK) in the regulation of cardiac hypertrophy
Bibliographic record
Abstract
Backgrond: The polyphenol resveratrol has been attributed to some of the cardioprotective effects of red wine consumption, including the ability to inhibit hypertrophy via its antioxidant properties. A recent discovery in hepatocytes showed that resveratrol can activate AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis. However, it is currently unknown whether resveratrol can also activate cardiac AMPK and the functional consequence of this. As we have shown that activation of AMPK inhibits protein synthesis associated with cardiac hypertrophy, we hypothesized that an additional mechanism by which resveratrol inhibits hypertrophy is via AMPK activation. Methods: To investigate this, neonatal rat cardiac myocytes were treated with vehicle (Veh) or 50 µM resveratrol (Resv) for 24 hours and 10 µM phenylephrine (PE) to induce hypertrophy. Contributors of the hypertrophic response, such as protein synthesis and specific intracellular signalling pathways, were measured using [3H]-phenylalanine incorporation and immunoblot analysis, respectively. Results: Activation of AMPK was achieved with resveratrol even in the presence of phenylephrine, as shown by increased AMPK phosphorylation (Veh+PE = 0.69±0.06 vs Resv+PE = 1.57±0.29 arbitrary units, p < 0.01). Resveratrol also significantly decreased protein synthesis induced by phenylephrine (Veh+PE = 45702.5±5252.9 vs Resv+PE = 32929.0±4512.9 disintegrations per minute, p < 0.05). This was associated with reduced activities of regulators of protein synthesis, namely p70S6 kinase and eukaryotic elongation factor-2 (eEF2). Specifically, resveratrol countered the effects of phenylephrine by blunting the increase in p70S6 kinase phosphorylation while partially restoring eEF2 phosphorylation. Furthermore, resveratrol dramatically decreased nuclear factor of activated T-cells (NFAT) promoter activity, as shown by reduced luciferase activity driven by a NFAT-responsive promoter (Veh+PE = 171100±7881 vs Resv+PE = 27530±5975 luciferase activity, p < 0.001). Conclusions: As the calcineurin-NFAT pathway is thought to be involved in pathological hypertrophy, this provides further evidence that AMPK activation has therapeutic potential, and shows another mechanism by which resveratrol can prevent hypertrophic growth.
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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 | 0.001 |
| 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".