38 Epoxyeicosatrienoic acid protect mitochondrial functions and dynamics during in vitro cellular stress
Bibliographic record
Abstract
Rationale Epoxyeicosatrienoic acid (EETs), cytochrome P450 derived metabolites of arachidonic acid, are vital in maintaining cardiac homeostasis. Previously, we demonstrated that EETs mediated cardiac protection involved preserving mitochondrial integrity and attenuating the opening of mitochondrial permeability transition pore. In this study, we aimed to further investigate EETs-mediated mitochondrial protection during cellular stress. Methodology Isolated mice hearts were subjected to global ischemia-reperfusion using Langendorff technique. Human fibroblast WI-38 cells and rat myocardial H9c2 cells were treated with 11,12-EET (0 or 1μM) and subjected to different types of cellular stressors including hypoxia-reoxygenation (HR), acute doxorubicin (DOX) treatment and photodynamic stress (PD). Alteration in mitochondrial function and dynamics were monitored with epifluorescence microscopy. Levels and activity of mitochondrial dynamics proteins DRP1 and OPA1 were assessed by western blotting while caspase-3 activity was determined as apoptotic marker. Results Significant mitochondrial depolarisation during reoxygenation was prevented by EETs. DOX treatment resulted in both increased mitochondrial fragmentation and membrane depolarisation. These effects were significantly reduced by EETs. EETs attenuated the activation of caspase-3, downstream to mitochondrial dysfunction, following DOX treatment. Similarly, EETs enhanced mitochondrial resistance and maintained their membrane potential and elongated morphology during photo-activated cytotoxicity. EETs inhibited DRP1 during ischemia reperfusion leading to delayed fragmentation. Conclusions EETs slowed the collapse of mitochondrial membrane potential following HR injury, DOX treatment and PD stress. EETs minimised mitochondrial fragmentation induced by DOX and PD treatments by inhibiting DRP1 and preserving OPA1. Together these data suggest that EETs can enhance mitochondrial function against cellular stress and improve their survival.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".