Hypoxic stress‐induced changes in adrenergic function: role of HIF1α
Bibliographic record
Abstract
Sustaining epinephrine-elicited behavioral and physiological responses during stress requires replenishment of epinephrine stores. Egr-1 and Sp1 contribute by stimulating the gene encoding the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT), as shown for immobilization stress in rats in adrenal medulla and for hypoxic stress in adrenal medulla-derived PC12 cells. Hypoxia (5% O(2)) also activates hypoxia inducible factor (HIF) 1alpha, increasing mRNA, nuclear protein and nuclear protein/hypoxia response element binding complex formation. Hypoxia and HIF1alpha over-expression also elevate PNMT promoter-driven luciferase activity in PC12 cells. Hypoxia may be limiting as HIF1alpha over-expression increases luciferase expression to no greater extent than oxygen reduction alone. HIF1alpha inducers CoCl(2) or deferoxamine elevate luciferase as well. PC12 cells harboring a HIF1alpha expression construct show markedly higher levels of Egr-1 and Sp1 mRNA and nuclear protein and PNMT mRNA and cytoplasmic protein. Inactivation of Egr-1 and Sp1 binding sites in the proximal -893 bp of PNMT promoter precludes HIF1alpha stimulation while a potential hypoxia response element (-282 bp) in the promoter shows weak HIF1alpha affinity at best. These findings are the first to suggest that hypoxia activates the proximal rat PNMT promoter primarily via HIF1alpha induction of Egr-1 and Sp1 rather than by co-activation by Egr-1, Sp1 and HIF1alpha. In addition, the rise in HIF1alpha protein leading to Egr-1 and Sp1 stimulation of PNMT appears to include HIF1alpha gene activation rather than simply prevention of HIF1alpha proteolytic degradation.
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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) | 0.001 | 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".