CRF and urocortin 3 protect the heart from hypoxia/reoxygenation-induced apoptosis in zebrafish
Bibliographic record
Abstract
Fish routinely experience environmental hypoxia and have evolved various strategies to tolerate this challenge. Given the key role of the CRF system in coordinating the response to stressors and its cardioprotective actions against ischemia in mammals, we sought to characterize the cardiac CRF system in zebrafish and its role in hypoxia tolerance. We established that all genes of the CRF system, the ligands CRFa, CRFb, urotensin 1 (UTS1), and urocortin 3 (UCN3); the two receptor subtypes (CRFR1 and CRFR2); and the binding protein (CRFBP) are expressed in the heart of zebrafish: crfr1 > crfr2 = crfbp > crfa > ucn3 > crfb > uts1. In vivo, exposure to 5% O2saturation for 15 min and 90 min of recovery resulted in four- to five-fold increases in whole heart crfb and ucn3 mRNA levels but did not affect the gene expression of other CRF system components. In vitro, as assessed by monitoring caspase 3 activity and the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells, pretreatment of excised whole hearts with CRF or UCN3 for 30 min prevented the increase in apoptosis associated with exposure to 1% O2saturation for 30 min with a 24-h recovery. Lastly, the addition of the nonselective CRF receptor antagonist αh-CRF(9–41)prevented the cytoprotective effects of CRF. We show that the CRF system is expressed in fish heart, is upregulated by hypoxia, and is cytoprotective. These findings identify a novel role for the CRF system in fish and a new strategy to tolerate hypoxia.
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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) | 0.001 | 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".