Nitric Oxide Upregulates Ferritin Synthesis Independently of Iron Regulatory Protein-Iron Responsive Element Binding Activity.
Bibliographic record
Abstract
Abstract The remarkable post-transcriptional regulation of intracellular iron homeostasis by iron regulatory proteins 1 and 2 (IRP1 and IRP2) is touted as a classic example of translational control. During low levels of intracellular iron, IRPs bind to specific nucleotide sequences known as iron responsive elements (IRE) present in the 5′-untranslated region (UTR) of ferritin (Ft) mRNA and the 3′UTR of transferrin receptor (TfR) mRNA. Such binding during conditions of low intracellular iron, blocks the translation of Ft, the ubiquitous and major iron storing protein, while TfR mRNA is stabilized, leading to increased TfR synthesis and iron uptake. High levels of intracellular iron will abrogate IRP-IRE binding activity, de-repressing Ft translation on the one hand, while causing TfR mRNA instability on the other. This system ensures that potentially hazardous iron is safely stored when it is in abundance and acquired when its levels are low. Nitric oxide (NO), a gaseous molecule involved in a myriad of functions, is known to affect the IRP system in many ways. The NO+ redox form of nitric oxide is involved in the reversible post-translational regulation of numerous proteins (including IRP2), a process called S-nitrosylation. We previously reported that NO+ causes upregulation of Ft synthesis along with IRP2 degradation. Here we report that sodium nitroprusside (SNP), an NO+ donor, causes a dramatic and rapid increase of ferritin synthesis that for a time occurs without interfering with IRP-IRE binding activities. We also show that NO+ increases the translational efficiency of ferritin mRNA as compared to treatment with ferric ammonium citrate, an iron donor. In addition, we also report that SNP does not function as an iron donor. These results indicate that NO+-mediated upregulation of ferritin synthesis is, in part, due to an IRP-independent post-transcriptional mechanism of regulation.
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".