Calcein and the Labile Iron Pool.
Bibliographic record
Abstract
Abstract The labile iron pool is a putative cytosolic compartment of loosely bound, redox-active, chelator-accessible iron. Iron contained within this pool is thought to influence the activity of iron regulatory proteins (IRPs), which bind to iron response elements (IRE) during low iron conditions; this association blocks the translation of ferritin mRNA, and stabilizes transferrin receptor mRNA. High levels of labile iron have been shown to promote oxidative stress. As this pool has such profound effects upon cellular iron homeostasis, there has been great interest in the development of methods to measure labile iron. Calcein, a fluorescent iron chelator, has been widely used to monitor the labile iron pool. When the non-fluorescent acetoxymethyl ester moiety (calcein-AM), enters cells, it is immediately cleaved by cytosolic esterases to its cell-impermeable, fluorescent calcein form. Iron binding to calcein quenches its fluorescence, which can subsequently be recovered following the loss of its iron to a stronger chelator. The difference in fluorescence between the bound and unbound calcein forms is thought to be proportional to the labile iron pool itself. While this method has been commonly exploited, it is unknown whether calcein may over-estimate the size of the labile pool by stripping iron from sources where it may be loosely bound, or by intercepting iron during its passage from one compartment to another. Although it is believed that calcein exerts very little direct influence on cellular iron homeostasis and acts only as a passive sensor of labile iron, some recent evidence from our lab indicates that this may not be the case. We have observed that incubation with calcein results in the activation of IRP-2 and stabilization of HIF-1α, a potent physiological regulator governing the expression of genes involved in oxygen sensing and iron metabolism. Furthermore, we have found that the size of the labile iron pool as measured by calcein was proportional to the amount of calcein loaded in HeLa and K562 cell lines. These findings suggest that calcein may be able to perturb cellular iron homeostasis, and may not accurately reflect the size of the labile iron pool. While calcein may still be used for comparative purposes under identically controlled conditions, its usefulness as a quantifying agent should be regarded with caution.
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".