Ca2+ Inhibits Reactive Oxygen Species Scavenging in Naked Mole-Rat Cortical Homogenates
Bibliographic record
Abstract
Deleterious perturbations in reactive oxygen species (ROS) and calcium (Ca 2+ ) handling are key initiators of cell death in hypoxia-intolerant mammalian brain. Elevated cellular Ca 2+ can also inhibit ROS scavengers, exacerbating the deleterious impact of hypoxia on redox homeostasis. Conversely, such perturbations are typically absent in the brain of hypoxia-tolerant animals, including naked mole-rats (NMRs; Heterocephalus glaber ), in which a remarkable ability to scavenge ROS has been observed in cardiac and skeletal muscle. We asked if NMR brain possesses a similar ability to detoxify ROS and whether Ca 2+ impairs ROS scavenging in NMR brain. To test these questions, we used the Amplex ultrared assay to measure the impact of Ca 2+ on the ability of NMR brain homogenates to detoxify a bolus (50 µl of 10 µm H 2 O 2 ) of exogenously applied H 2 O 2 during different states of mitochondrial respiration. We report that (1) NMR brain mitochondria are net consumers of H 2 O 2 , (2) thioredoxin reductase is a major contributor to this scavenging capacity, and (3) Ca 2+ inhibits ROS scavenging in all conditions tested. The rate of ROS consumption by NMR cortical homogenates is considerably greater than previously published measurements from rat and mouse brain and is less sensitive to inhibition by exogenous Ca 2+ , suggesting that NMRs have evolved an enhanced capacity to detoxify ROS. This ability is likely neuroprotective in this animal, which experiences regular bouts of intermittent hypoxia and reoxygenation of varying severity in its natural underground burrow habitat.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".