Nitric oxide reduces vascular smooth muscle cell elastase activity through cGMP‐mediated suppression of ERK phosphorylation and AML1B nuclear partitioning
Bibliographic record
Abstract
Nitric oxide (NO) reduces the severity of pulmonary vascular disease in rats as do elastase inhibitors. We therefore hypothesized that NO inhibits elastase by suppressing mitogen‐activated protein kinases that trans ‐activate AML1B, a transcription factor for elastase. We used cultured pulmonary artery smooth muscle cells in which serum‐treated elastin (STE) induces a > threefold increase in elastase activity as evaluated by solubilization of [ 3 H]‐elastin. NO donors (SNAP and DETA NONO‐ate) inhibited elastase in a dose‐dependent manner as did a cGMP mimetic (8‐pCPT‐cGMP). SNAP inhibition of elastase was reversed by coadministration of a cGMP‐PKG inhibitor (Rp‐8‐pCPT‐cGMP). The STE‐induced increase in phospho‐ERK was suppressed by NO donors and the cGMP mimetic, and reversed by cGMP‐PKG inhibitor, as was expression of AML1B and DNA binding in nuclear extracts. A concomitant increase in p38 phosphorylation was also inhibited by SNAP, but whereas MEK inhibitor (PD98059) suppressed elastase and AML1B‐DNA binding, a p38 inhibitor (SB202190) did not. Our study uniquely links NO with inhibition of elastase‐dependent matrix remodeling in vascular disease by suggesting a cGMP‐PKG‐related mechanism suppressing ERK‐mediated partitioning of AML1B in nuclear extracts.—Mitani, Y., Zaidi, S. H. E., Dufourcq, P., Thompson, K., Rabinovitch, M. Nitric oxide reduces vascular smooth muscle cell elastase activity through cGMP‐mediated suppression of ERK phosphorylation and AML1B nuclear partitioning. FASEB J. 14, 805–814 (2000)
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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 | 0.000 | 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) | 0.000 | 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".