Induction of hypoxia inducible factor 2α (HIF‐2α) may be dependent on mitochondrial O <sub>2</sub> consumption in an immortalized adrenomedullary chromaffin cell line
Bibliographic record
Abstract
Under normal O 2 levels, hypoxia inducible factor (HIF) ‐2α is hydroxylated via a set of oxygen‐dependent prolyl hydroxylases and degraded. During hypoxia, HIF‐2α is stabilized and translocates to the nucleus where it regulates genes critical for survival in low O 2 . The mechanisms by which HIF‐2α is stabilized during hypoxia remain controversial. To address this, we are using an O 2 ‐sensitive immortalized rat adrenomedullary chromaffin (MAH) cell line. In MAH cells, HIF‐2α induction occurs within 15 min exposure to hypoxia (2% O 2 ) and remains elevated for at least 24 hrs. This induction is blocked in the presence of rotenone (1 μM), myxothiazol (1 μM) and NaCN (1 mM), which inhibit mitochondrial complexes I, III, and IV, respectively. In addition, mitochondria‐deficient (ρ0) MAH cells fail to induce HIF‐2α during hypoxia (2% O 2 , 1 hr). The inhibitory effects of rotenone appear to be dependent on O 2 concentration. At higher O 2 levels (5%), HIF‐2α induction is inhibited by low concentrations of rotenone (10 nM), that are ineffective at lower O 2 levels (2%). We propose that mitochondrial O 2 consumption during hypoxia lowers or depletes cytoplasmic O 2 concentration, permitting HIF‐2α stabilization. Blocking mitochondrial respiration increases cytoplasmic O 2 concentration and triggers HIF‐2α degradation. Supported by the Heart and Stroke Foundation of Ontario and Canada
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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 | 0.000 |
| 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 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".