Matrix metalloproteinase‐2 contributes to hydrogen peroxide induced cardiac myocyte apoptosis
Bibliographic record
Abstract
Reperfusion of the ischemic heart triggers the biosynthesis of reactive oxygen species that damage the myocardium and trigger myocyte apoptosis. Matrix metalloproteinase (MMP)‐2 is activated during ischemia‐reperfusion injury and mediates contractile dysfunction by proteolyzing novel intracellular targets. We hypothesized that MMP‐2 may be a mediator of apoptosis by cleaving Bid. Neonatal rat cardiac myocytes were treated with 200 μM H 2 O 2 +/− MMP inhibitors (50 μM o‐phenanthroline or 1 nM tissue inhibitor of metalloproteinase‐2). H 2 O 2 ‐induced apoptosis was preceded by early permeabilization of the sarcolemma and reduction in mitochondrial membrane potential; with delayed activation of caspase 3 and DNA fragmentation. MMP inhibitors significantly reduced H 2 O 2 ‐induced apoptotic cell death. H 2 O 2 caused an increase in MMP‐2 activity in cell lysates. Incubation of Bid with MMP‐2 (4 hr, 37°C) resulted in its cleavage and those cleaved fragments induced cytochrome C release from isolated mitochondria, similar to caspase‐8 or calpain cleaved Bid. These data suggest that MMP‐2 may be a novel mediator of H 2 O 2 ‐induced apoptotic signalling through proteolytic activation of Bid, a pathway that can be abolished by MMP inhibitors.
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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) | 0.001 | 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) | 0.002 | 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".