Platelet cell-surface protein disulphide-isomerase mediated <i>S</i>-nitrosoglutathione consumption
Bibliographic record
Abstract
S-nitrosothiols (RSNOs) regulate several aspects of platelet physiology including inhibition of activation, adhesion and aggregation. PDI (protein disulphide-isomerase) has recently been found to be localized to the cell surface, where it exhibits both disulphide-exchange and denitrosation activities. The disulphide-exchange activity of PDI has been linked to aspects of platelet aggregation. The present study suggests that the metabolism of RSNOs by platelets is a function of PDI denitrosation activity. Exposure of washed human platelets to increasing concentrations of GSNO (S-nitrosoglutathione) resulted in saturable denitrosation kinetics. The presence of known PDI inhibitors phenylarsine oxide and anti-PDI antibodies prevented GSNO denitrosation. The fact that, in the presence of GSNO plus the cell-permeable guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxaline-1-one, the initial rates of ADP-induced platelet aggregation and the maximum DeltaOD were diminished by approximately 40% shows that RSNOs have dual inhibitory effects on platelets, which are mediated through PDI. First, PDI denitrosates RSNOs, releasing NO that, via the guanylate cyclase/G-kinase route, attenuates platelet activation. Secondly, RSNOs are denitrosated at the same PDI-active site that catalyses the disulphide bond formation between integrins and their ligands, thereby attenuating irreversible aggregation.
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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 | 0.000 |
| 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".