Role of reactive oxygen species in the neural and hormonal regulation of the PNMT gene in PC12 cells
Bibliographic record
Abstract
In adrenergic cells norepinephrine is N‐methylated by the enzyme phenylethanolamine N‐methyltransferase (PNMT) to produce epinephrine. Prior studies have demonstrated that the PNMT gene in adrenal chromaffin cells may be regulated hormonally via the hypothalamic‐pituitary‐adrenal axis and neurally via stimulation of the splanchnic nerve. Further, hypoxia has been shown to play a key role in the regulation of PNMT. The purpose of this study was to examine the impact of reactive oxygen species (ROS) produced by the hypoxia mimetic agent CoCl 2 on the hormonal and neural stimulation of PNMT. RT‐PCR analyses show inductions of the PNMT intron‐retaining and intronless mRNA splice variants by CoCl 2 (3.0‐ and 1.76‐fold respectively). Transient transfection assays of cells treated simultaneously with CoCl 2 and dexamethasone show increased promoter activity (18.5‐fold), while mRNA levels of both splice variants do not demonstrate synergistic effects. Similar results were observed when investigating the effects of CoCl 2 ‐induced ROS on the neural stimulation of PNMT. Our findings demonstrate that CoCl 2 ‐induced ROS have synergistic effects on the hormonal and neural activation of the PNMT promoter and suggest post‐transcriptional regulation of PNMT following hormonal or neural activation during hypoxia. This study was funded by the Natural Sciences and Engineering Research Council of 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 | 0.001 |
| 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".