Inhibitory effects of caspase inhibitors on the activity of matrix metalloproteinase (MMP)‐2
Bibliographic record
Abstract
Matrix metalloproteinase (MMP)‐2 plays a harmful role during the onset of ischemia and reperfusion (I/R) in the heart. Caspases are a group of cysteine‐dependent aspartate‐directed proteases which regulate cellular apoptosis. The role of caspase activity in I/R is controversial, but there are protective effects of caspase inhibitors which are independent of apoptosis. The protective actions of caspase or MMP inhibitors in ameliorating I/R injury had led us to hypothesize that caspase inhibitors also reduce MMP‐2 activity. In vitro degradation assay using human recombinant MMP‐2 and troponin I (TnI) as its substrate showed that caspase inhibitors (Z‐IE(OMe)TD(OMe)‐fmk, Ac‐DEVD‐CHO, Ac‐LEHD‐cmk, Z‐VAD‐ fmk, Ac‐YVAD‐cmk), in comparison to a bond fide MMP inhibitor, significantly inhibited MMP‐2‐mediated TnI degradation in a concentration‐dependent manner (10 μM: p<0.0003 and 30 μM: p<0.0001 vs. DMSO control). A quantitative kinetic assay using a fluorogenic MMP substrate revealed that these caspase inhibitors blocked MMP‐2 activity in a concentration‐dependent manner with similar IC50 (all values in μM range). Inhibition of MMP‐2 activity may be an additional pharmacological action which could contribute to the protective effects of caspase inhibitors seen in heart injury models. Canadian Institutes for Health Research, Heart & Stroke Foundation of Canada and Alberta Innovates – Health Solutions.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.002 | 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".