Abstract 5553: S100A1 Modulates Endothelial Nitric Oxide Availability by Co-ordinate Regulation of Nitric Oxide Synthase Phosphorylation and Gene Expression of Related Signaling Molecules
Bibliographic record
Abstract
Background: S100A1, a Ca 2+ -sensor protein in endothelial cell, regulates endothelial function. S100A1 knockout mice (KO) are hypertensive with impaired nitric oxide (NO) production and endothelial-dependent vasodilatation. We examine the impact of S100A1 on phosphorylation of Ser 1177 and Thr 495 , positive and negative regulatory residues, respectively, in endothelial nitric oxide synthase (eNOS) and on expression of diverse genes involved in eNOS signaling. Methods and Results: Endothelial cells (EC) were isolated and from pulmonary vasculature of wild-type (WT) and KO mice. WT EC exhibited higher proliferative rates than KO measured by WST-method, and expressed as absorbance/5000 cells/well (0.8923±0.091 vs. 0.268±0.055, p<0.05, n=3) and higher NO production (2214.00±1016.17 vs. 566.75±243.79 nM, p<0.05, n=6). Lower eNOS activity in KO was associated with higher and lower basal phosphorylation at Thr 495 and Ser 1177 , respectively. Bradykinin (100 nM) resulted in rapid (1 minute) 3-fold higher maximal phosphorylation of Ser 1177 in WT vs. KO with equivalent rapid dephosphorylation of Thr 495 in both cell types. By contrast, acetylcholine (10 μ M) at 30 seconds produced more robust dephosphorylation of Thr 495 in WT compared to KO, with comparable effects on Ser 1177 phosphorylation. In KO versus WT EC, PCR microarray analysis demonstrated greater than 2-fold increase in mRNA expression of caveolin-1, NADPH oxidase 1, glutathione peroxidase, and calmodulin-1. KO EC exhibited a 5-fold reduction in eNOS mRNA, confirmed by a reduction in eNOS protein (4.02±0.19 fold, n=3). Conclusion: Absence of S100A1 in endothelial cells results in impaired proliferation, decreased NO availability, and regulation of gene expression that contributes or, alternately, compensates for this phenotype. Lack of S100A1 also impairs co-ordinated eNOS phosphorylation at baseline, and in response to agonists, that augments NO production. Thus, S100A1 plays a multifactorial and novel role in controlling NO synthesis and the endothelial phenotype.
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) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
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".