Cardiac Actin Capping Protein Reduction and Protein Kinase C Inhibition Maintain Myofilament Function During Cardioplegic Arrest
Bibliographic record
Abstract
BACKGROUND: Heart transplantation is associated with cold, cardioplegic arrest that impairs myocardial function. Protein Kinase C (PKC) suppression of myofilaments may contribute to this dysfunction. CapZ-deficient cardiac myofilaments are unresponsive to PKC. We hypothesized that myofilaments from CapZ-deficient transgenic hearts are resistant to cardioplegic dysfunction and that PKC inhibition improves function. METHODS: Heart function was assessed using a Langendorff apparatus. Myofilaments isolated from murine hearts were assessed with an actomyosin MgATPase assay and protein phosphorylation gels. PKC activation was examined by immunoblotting. RESULTS: Wildtype hearts showed impaired function after cardioplegic arrest. CapZ-deficient transgenic mouse hearts performed significantly better after 1 h cardioplegia than wildtype hearts, but not after 4 h cardioplegic arrest. Wildtype myofilaments had depressed activation at 1 and 4 h cardioplegic arrest, as demonstrated by reduced actomyosin MgATPase activity. CapZ-deficient myofilaments showed no reduced actomyosin MgATPase activity at either time. Troponin I (TnI) phosphorylation increased by approximately 20% at 1 and 4 h in wildtype mice. Myosin binding protein C (MyBP-C),and troponin T (TnT) phosphorylation increased by less than 10% at 1 h, and tended to rise at 4 h. Myofilament protein phosphorylation was largely unchanged in CapZ-deficient hearts at 1 h, but MyBP-C tended to be dephosphorylated at 4 h cardioplegic arrest. Myofilament-associated PKC-α, -βII, -δ, and -e increased at 1 and 4 h cardioplegia in wildtype hearts, whereas only PKC-α increased in transgenic myofilaments at 1 h. PKC inhibition abolished the cardioplegic-dependent changes in actomyosin MgATPase activity and TnI phosphorylation of wildtype myofilaments. CONCLUSIONS: We demonstrate a direct link between PKC activation and myofilament dysfunction associated with cold, cardioplegic arrest. Moreover, we show for the first time a cardioprotective benefit of decreased cardiac CapZ.
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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 | 0.001 |
| 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".