Roles of reactive oxygen species in angiopoietin‐1/tie‐2 receptor signaling
Why this work is in the frame
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Bibliographic record
Abstract
In this study we identified the involvement of reactive oxygen species (ROS) in signaling and biological effects of the angiopoietin-1 (Ang-1)/tie-2 receptor pathway. Exposure of human umbilical vein endothelial cells to Ang-1 (50 ng/ml) induced rapid and transient production of ROS, particularly superoxide anions. ROS production was attenuated by preincubation with a peptide (gp91ds-tat) that inhibits the association of the gp91(phox) subunit with the p47(phox) subunit of NADPH oxidase and by the expression of a dominant-negative form of Rac-1 (Rac1N17). These results suggest that ROS production in response to Ang-1 exposure originates mainly from a Rac-1-dependent NADPH oxidase. Overexpression of antioxidants (superoxide dismutase and catalase) and Rac1N17, as well as preincubation with selective inhibitors of NADPH oxidase augmented basal p38 phosphorylation, inhibited Ang-1-induced PAK-1 phosphorylation and potentiated Ang-1-induced Erk1/2 phosphorylation but had no influence on AKT and SAPK/JNK phosphorylation by Ang-1. Exposure to Ang-1 (100 ng/ml) for 5 h induced a threefold increase in endothelial cell migration, a response that was strongly inhibited by overexpression of antioxidants, Rac1N17, and selective NADPH oxidase inhibitors. We conclude that activation of tie-2 receptors by Ang-1 triggers the production of ROS through activation of NADPH oxidase and that ROS generation by Ang-1 promotes endothelial cell migration while negatively regulating Erk1/2 phosphorylation.
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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 it