Calpain inhibition by calpeptin does not prevent APLT activity reduction in PS-exposing platelets, but calpeptin has independent pro-apoptotic effects
Bibliographic record
Abstract
Exposure of procoagulant phosphatidylserine (PS) on the surface of activated platelets is not readily reversible and this may propagate thrombosis. Persistence of PS exposure may be attributed, at least in part, to a continued reduction of the activity of aminophospholipid translocase (APLT), that transports PS from the outer to the inner membrane leaflet. We investigated whether calpain is involved in the inhibition of APLT activity. In flow cytometric investigations, using the inhibitors calpeptin or E64d at a concentration that blocks calpain activation, we found that calpain is not responsible for the reduction in APLT activity that results in persistence of PS exposure. Unexpectedly, we found that the inhibitors had additional effects independent of blocking calpain. Incubation of resting platelets with calpeptin resulted in a subpopulation of platelets with increased intracellular Ca(2+) and persistent PS exposure. The inhibitors also increased the proportion of platelets with persistent PS exposure in suspensions stimulated with thrombin and/or collagen or the Ca(2+)-ionophore A23187 under conditions in which calpain was not activated or in which its activation was completely blocked; P-selectin expression on thrombin and/or collagen-stimulated platelets was inhibited. Furthermore, in stimulated platelets, calpeptin increased the proportion of the PS-exposing platelets expressing a second apoptotic hallmark, collapsed mitochondrial inner membrane potential (DeltaPsi(m)). These additional effects of calpeptin on platelet regulation of intracellular Ca(2+) levels and apoptotic-like events should be taken into account when it is used as an inhibitor of calpain.
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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) | 0.001 | 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) | 0.001 | 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".