Propofol Reduces Apoptosis and Up-Regulates Endothelial Nitric Oxide Synthase Protein Expression in Hydrogen Peroxide-Stimulated Human Umbilical Vein Endothelial Cells
Bibliographic record
Abstract
In Brief BACKGROUND: Vascular endothelial cells play an important role in maintaining cardiovascular homeostasis. Oxidative stress is a critical pathogenic factor in endothelial cell damage and the development of cardiovascular diseases. In this study we evaluated the effects of propofol on oxidative stress-induced endothelial cell insults and the role of serine–threonine kinase Akt modulation of endothelial nitric oxide synthase (eNOS) as a mechanism of protection. METHODS: Human umbilical vein endothelial cells were used as the experimental model. Hydrogen peroxide (H2O2, 100 μM) was used as the stimulus of oxidative stress. Study groups included 1) control; 2) cells incubated with H2O2 alone; 3) cells incubated with propofol (50 μM) alone; or 4) cells pretreated with propofol 50 μM for 30 min then co-incubated with H2O2. Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Trypan blue dye exclusion test. Cell apoptosis was evaluated by Hoechst 33258 staining. Caspase-3 activity was determined by the colorimetric CaspACE™ Assay System. Expressions of Akt, phospho-Akt, and eNOS were detected by Western blotting. RESULTS: H2O2 decreased cell viability, induced apoptosis, and increased caspase-3 activity in human umbilical vein endothelial cells. Propofol significantly protected cells from H2O2-induced cell damage, apoptosis and decreased H2O2-induced increase in caspase-3 activity. Propofol treatment significantly increased eNOS expression compared to control and H2O2-stimulated cells. There was no significant difference in phospho-Akt (Ser 473 or Thr 308) expression among the groups. CONCLUSIONS: Propofol 50 μM can reduce H2O2-induced damage and apoptosis in endothelial cells, by suppressing caspase-3 activity and by increasing eNOS expression via an Akt-independent mechanism. IMPLICATIONS: We evaluated the effects of propofol on oxidative stress-induced endothelial cell insults and the possible protection by Akt modulation of endothelial nitric oxide synthase (eNOS). Our results show that propofol can reduce hydrogen peroxide-induced damage and apoptosis in endothelial cells, by suppressing caspase-3 activity and increasing eNOS expression via an Akt-independent mechanism.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".