Epoxyeicosatrienoic Acids and/or Their Metabolites Promote Hypoxic Response of Cells
Bibliographic record
Abstract
Epoxyeicosatrienoic acids (EETs), including 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET, are produced by cytochrome P450 (P450) such as CYP2C8 and 2C9; and they are hydrolyzed to dihydroxyeicosatrienoic acids (DHETs) by epoxide hydrolase. Particular interest in the epoxygenase reaction has developed because of the potent biological activities (modulation of vascular tone and anti-inflammatory activity, etc.) attributed to EETs. We focused on a new biological function of EETs and DHETs, which induce vascular endothelial growth factor (VEGF) and erythropoietin (EPO) under hypoxia. Human hepatoma cells, Hep3B, and human umbilical artery endothelial cells (HUAEC) were used in this study. An inhibitor of phospholipase A(2), methyl arachidonyl fluorophosphonate (MAFP), and inhibitors of P450s inhibited the VEGF and EPO induction of HUAEC and Hep3B, respectively, under hypoxia. Overexpression of CYP2C8 in Hep3B induced EPO and VEGF under hypoxia. Sulfaphenazole, an inhibitor of CYP2C8/2C9 suppressed luciferase promoter activity with the hypoxia response element (HRE) of VEGF in HUAEC. Exogenous 11,12-EET and 14,15-DHET induced reporter activity in HUAEC and Hep3B cells concomitant with increased levels of hypoxia-inducible factor-1alpha (HIF-1alpha), which is a key factor in the hypoxia response, but 11,12-DHET and 14,15-EET did not. These results suggested that EETs and DHETs play an important role in the hypoxia response of cells.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".