Abstract 209: Role Of Apoptosis Inducing Factor In Caspase-independent Apoptosis In Hypertrophic Cardiomyocytes
Bibliographic record
Abstract
Caspases are thought to be central mediators of the apoptotic program, but recent data indicate that apoptosis can also be activated by caspase-independent mechanisms, such as via apoptosis inducing factor (AIF). We and others have shown that the hypertrophic heart may be more prone to apoptotic insult. Thus, we seek to investigate the characteristics of AIF-induced cardiac apoptosis in hypertrophic cardiomyocytes in vitro and describe its role. Method: Hypertrophic (H-CMs) and non-hypertrophic cardiomyocytes (N-CMs) were isolated from Dahl salt sensitive rats fed a high salt or a normal diet for 6 weeks, respectively; exposed to apoptotic stimulation, such as hypoxia/reoxygenation (H/R) or staurosporine (ST); and analyzed for the activation of caspases, AIF and cytochrome c release from mitochondria, and the rate of apoptosis. Results: Both H-CMs and N-CMs responded to H/R and ST with a significant release of AIF (evidence of AIF activation), cytochrome c (evidence of caspase-dependent apoptosis), and apoptosis. Apoptotic stimuli did not cause significant caspase activation in H-CMs, but the release of AIF from the mitochondria in these cells was a significant 2.5 times greater than in N-CMs. These results suggest that AIF-induced apoptosis is more prominent in H-CMs. We also found that in N-CMs, inhibiting caspase by adenoviral overexpression of CrmA (a known caspase inhibitor), or pre-treatment with zVAD-fmk (a pan-caspase inhibitor) significantly blocked apoptosis after H/R and ST (39% and 66%, p Conclusion: Apoptotic mechanisms in hypertrophic cardiomyocytes appear to be biased towards caspase independent pathways, and therefore the inhibition of AIF-induced apoptosis may be an effective anti-apoptotic therapy in hypertrophic heart.
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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) | 0.000 | 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) | 0.003 | 0.001 |
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".