Abrupt Reoxygenation of Microvascular Endothelial Cells After Hypoxia Activates ERK1/2 and JNK1, Leading to NADPH Oxidase‐Dependent Oxidant Production
Why this work is in the frame
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Bibliographic record
Abstract
OBJECTIVE: Mitogen-activated protein kinases (MAPK) in microvascular endothelial cells (EC) may participate in organ pathophysiology following hypoxia/reoxygenation (H/R). The authors aimed to determine the role of MAPK in H/R-induced reactive oxygen species (ROS) generation in mouse microvascular EC. METHODS: Cultured EC derived from skeletal muscle of male wild-type (WT), gp91phox-/- or p47phox-/- mice were subjected to hypoxia (0.1% O2, 1 h) followed by abrupt reoxygenation, H/RA (hypoxic medium quickly replaced by normoxic medium), or slow reoxygenation, H/RS (O2 diffused to cells through hypoxic medium). Cells were analyzed for ERK, JNK, and p38 MAPK phosphorylation, NADPH oxidase activation, and ROS generation. RESULTS: In WT cells, H/RA but not H/RS rapidly phosphorylated ERK1/2 and JNK1 and subsequently increased ROS production. H/RA did not affect p38. MAPK phosphorylation persisted despite inhibition of NADPH oxidase, mitochondrial respiration, protein tyrosine kinase, or PKC. ROS increase during H/RA was prevented by deletion of gp91phox or p47phox, or MAPK inhibition. CONCLUSIONS: Abrupt reoxygenation after hypoxia activates ERK1/2 and JNK1 in mouse microvascular endothelial cells via a tyrosine kinase-, PKC-, and NADPH oxidase-insensitive mechanism, leading to increased NADPH oxidase-dependent ROS production. The results suggest that MAPK activation in the microvascular endothelium is O2-sensitive, contributing critically to tissue pathophysiology after H/R.
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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 | 0.001 | 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 | 0.000 |
| 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