Non-Heme Induction of HO-1 in Macrophages Does Not Apparently Alter Cellular Iron Levels.
Bibliographic record
Abstract
Abstract The catabolism of heme is carried out by members of the heme oxygenase (HO) family. The predominant isozyme in the digestion of erythroid heme is the inducible form, HO-1. The products of heme catabolism by HO-1 are ferrous iron, biliveridin (subsequently converted to bilirubin), and carbon monoxide (CO). In addition to its function in the recycling of erythrocyte iron, this microsomal enzyme has been implicated in a number of cytoprotective mechanisms mainly in the context of oxidant insult. HO-1 can be induced not only by heme, but also by cytokines, heat shock, metals, and other cellular stressors, especially those that generate reactive oxygen species (ROS). Implicit in all the reports of HO-1 cytoprotection to date are effects on the cellular handling of heme and , therefore, iron. While bilirubin is an antioxidant, ferrous iron is known to catalyze the production of hydroxyl radicals through Fenton chemistry. Thus, the release of iron from heme could be counterproductive in protecting the cell from oxidative stress. Furthermore, there are a number of non-heme stimulators of HO-1 induction, bringing to question the source of substrate for this enzyme in these paradigms. In the present study, HO-1 was induced by either sodium arsenite or hemin in the murine macrophage-like cell line, RAW264.7. Both of these inducers elicited a transient increase in both the mRNA and protein levels of HO-1, however, only hemin exposure induced an increase in the synthesis rate of the iron storage protein, ferritin. This increase in ferritin production rate, as measured by 35S-methionine incorporation, was attenuated by the HO inhibitor, tin-protoporphyrin IX (SnPP) as well as the cell permeable iron chelator, salicylaldehyde isonicotinoyl hydrazone (SIH). Additionally, treatment of the cells with hemin was able to elicit a decrease in the activity of iron regulatory proteins (IRPs) that could be blocked by preincubation with SnPP. Sodium arsenite had no effect on IRPs. These results suggest that iron released from hemin by HO-1 stimulates ferritin synthesis via the IRE/IRP system, while an increase in the enzyme via a non-heme inducer does not lead to iron release from endogenous heme sources.
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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) | 0.002 | 0.001 |
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".