Abstract 22: Calpain-Dependent Induction of Endoplasmic Reticulum Stress in Cardiomyocyte Apoptosis and Post--Myocardial Infarction Remodeling
Bibliographic record
Abstract
Background: Calpain is up-regulated and implicated in cardiomyocyte apoptosis and myocardial remodelling post myocardial infarction. Endoplasmic reticulum (ER) stress is induced and contributes to myocardial injury in a variety of cardiac diseases. This study was to investigate whether calpain plays a role in ER stress, thereby mediating apoptosis in cardiomyocytes and myocardial remodelling after infarction. Methods and Results: In rat cardiomyoblasts H9C2 cells, over-expression of calpain-1 increased the protein levels of Bip and CHOP, indicative of ER stress, and induced apoptosis determined by a decrease in Bcl-2 and increases in caspase-3 activation and DNA fragmentation. Inhibition of calpain activity or ER stress prevented apoptosis induced by calpain-1 over-expression. In contrast, over-expression of calpain-2 failed to induce apoptosis. The induction of ER stress by calpain-1 might be mediated through SERCA2a/Calcium signaling as up-regulation of calpain-1 reduced SERCA2a protein and elevated intracellular free Calcium in H9C2 cells. In a mouse model of myocardial infarction induced by coronary artery ligation, calpain activity was increased and ER stress was induced in the infracted heart. Up-regulation of calpastatin, the endogenous calpain inhibitor, inhibited calpain activation, prevented ER stress and apoptosis, reduced myocardial remodelling and improved myocardial function after infarction in calpastatin transgenic mice compared with their wild-type littermates. Conclusion: Calpain-1 induces ER stress through the proteolysis of SERCA2a, thereby mediating apoptosis in cardiomyocytes. Inhibition of calpain prevents ER stress and apoptosis, reduces myocardial remodelling and dysfunction after infarction. Thus, ER stress may represent a novel mechanism by which calpain mediates myocardial injury in the infracted heart.
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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 | 0.002 | 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) | 0.000 | 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".