The Activation of Matrix Metalloproteinease‐2 by Mitochondrially‐Generated Reactive Oxygen/Nitrogen Species
Bibliographic record
Abstract
Matrix metalloproteinase‐2 (MMP‐2), along with other MMPs, has been implicated in heart injury and disease. These pathologies are characterized by both acute and chronic oxidative stress. In vitro, low concentrations of reactive oxygen/nitrogen species (RONS) can directly activate MMP‐2 via post‐translational modifications. However, this has yet to be demonstrated in a living system. We investigated whether endogenous RONS produced by pharmacological inhibition of mitochondrial ubiquinol‐cytochrome c reductase with antimycin could increase MMP‐2 activity in cardiomyocyte and non‐cardiomyocyte cell lines. We exposed neonatal rat cardiomyocytes (NRVMs), H9c2 cardiomyoblasts and HT1080 fibrosarcoma cells to antimycin (0.01‐1, 0.3‐3.2 and 1‐100 µM for NRVMs, H9c2 and HT1080 respectively) in serum‐free media for short (0.5 h) or long (6 h) intervals to measure changes in MMP‐2 activity in cell lysates and conditioned media by gelatin zymography. The antimycin concentrations used did not affect viability or cell growth, but increased oxidative stress in a dose‐ and time‐dependent fashion as shown by decreased aconitase activity. Antimycin decreased lysate MMP‐2 activity in NRVMs, but increased it in H9c2 cells, despite comparable decreases in aconitase activity. HT1080 cells also exhibited increased MMP‐2 activities, but only at the lowest concentrations of antimycin used. The activity of secreted MMP‐2 was not consistently affected by antimycin treatment in any cell line. We conclude that intracellular MMP‐2 activity can be affected by endogenous oxidative stress in cultured cells, dependent upon cell type. This provides evidence that RONS could modulate MMP‐2 activity in vivo, independent of gene expression. Support: CIHR
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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".