Epigenetic regulation of phenylethanolamine N‐methyltransferase: implications for adrenaline biosynthesis
Bibliographic record
Abstract
Adrenaline, a neurohormone and neurotransmitter, plays an extensive role in the physiological response to stress, and the sympathetic regulation of blood pressure. Phenylethanolamine N‐methyltransferase (PNMT), the terminal enzyme in the catecholamine biosynthetic pathway, directly responsible for adrenaline synthesis, is elevated in hypertensive animals; genetic linkage studies have associated the PNMT gene to the development of hypertension. Epigenetic changes are heritable changes in gene expression that are a consequence of the modification of the DNA (methylation at CpG sites) or histones (e.g. by methylation, acetylation) that facilitate packaging the DNA into nucleosomes. Changes in the epigenome have been associated with incidences of cancer, metabolic disorders and cardiovascular pathologies. In this study, alteration in PNMT expression modifiable by epigenetic regulation was examined using the rat adrenal pheochromocytoma derived PC12 cells. In vitro methylation of a PNMT promoter driven luciferase construct, using CpG methylases, consequently lead to a radical decrease in promoter activation, even in presence of dexamethasone (Dex) or Forskolin (Fsk), otherwise potent activators of PNMT expression. Further, the influence of a DNA methylation inhibitor 5‐aza‐2′‐deoxycytidine (5aza2DC), and histone deacetylase inhibitor valproic acid (VPA) was examined. Transcript analysis of endogenous PNMT, and PNMT promoter driven luciferase assays, both revealed that PNMT transcription is elevated in presence of these epigenetic modifiers, and these compounds can interact with the activation by Dex or Fsk to modulate PNMT expression. The extent of CpG methylation at the promoter of PNMT using bisulphite‐sequencing, and transcription factor binding sites that are sensitive to epigenetic modification using site directed mutagenesis, are currently being examined. The data suggests that PNMT regulation is sensitive to epigenetic modification which can have repercussions for adrenaline biosynthesis, and consequently on its role as a neurotransmitter. Support or Funding Information CIHR
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".