Abstract 17483: Tert-butylhydroquinone Induces Gene Expression of Anti-oxidant Enzymes in Human Coronary Artery Endothelial Cells After Cyclosporine Treatment
Bibliographic record
Abstract
Introduction: Cyclosporine (CsA) is an important immunosuppressant; however it may lead to oxidative stress in coronary vasculature and subsequently cardiac allograft vasculopathy (CAV). We previously demonstrated that CsA impairs kinematics of the master antioxidant gene regulator - nuclear factor erythroid 2–related factor 2 (Nrf2) in Human Coronary Artery Endothelial Cells (HCAECs). Hypothesis: We assessed the hypothesis that tert-hydroquinone (tBHQ), an Nrf2 agonist, rescues CsA-mediated downregulation of antioxidant enzymes via increase in gene expression of Nrf2. Methods: HCAECs (n=6) were treated with 50μg/ml CsA ± 20μM tBHQ or tBHQ alone for 2 hours. Control (CON) groups received 0.1% DMSO. Quantitative-real time polymerase chain reaction was performed to assess gene expression of NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase-1 (HO-1), superoxide dismutase 1 (SOD1), and -2 (SOD2) at 2 hours. We also assessed Nrf2 gene expression at 2 hours. Results: Compared to control, CsA decreased the expression of NQO1, SOD1, and SOD2, but not HO-1. Exposure to tBHQ alone resulted in increased expression of NQO1, SOD2, and Nrf2, but not HO-1, and SOD1 compared to control. When cells were exposed to both tBHQ and CsA, we determined that expressions of NQO1, HO-1, SOD2 and Nrf2 were synergistically upregulated. Concomitant exposure to tBHQ partially restored the downregulated expression of SOD1 compared to CsA alone, but did not achieve control levels. Conclusion: Oxidative stress is increasingly known as a key component in pathogenesis of post-heart transplant coronary vasculopathy which is associated with morbidity and mortality. In conclusion, heart transplant patients who receive CsA therapy, may benefit from exposure to tBHQ since tBHQ-CsA co-therapy may mitigate coronary artery oxidative stress.
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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) | 0.004 | 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".