Abstract 17567: Stanniocalcin-1 Induces A Novel Anti-Oxidant Pathway in Cardiomyocytes
Bibliographic record
Abstract
Rationale: We have shown increased cardiac stanniocalcin-1 (STC1) in patients with idiopathic dilated cardiomyopathy. STC1 localizes to the inner mitochondrial, and transgenic overexpression of STC1 is associated with increased energy utilization. Objective: We examined the hypothesis that STC1 uncouples mitochondrial oxidative phosphorylation - to affect energy metabolism and superoxide generation in cardiomyocytes. Methods and Results: Compared to WT mouse heart, STC1 Tg heart displays 2-fold higher uncoupling protein 3 (UCP3) levels, 40% lower ATP levels, but similar activities of respiratory chain complexes I-IV. In cultured adult rat cardiomyocytes, recombinant hSTC1 is internalized by cultured rat cardiomyocytes and is targeted to the mitochondria within minutes; it induces UCP3, decreases mitochondrial membrane potential and suppresses baseline and ANG II-provoked superoxide generation. In freshly-isolated adult mouse cardiomyocytes, STC1 diminishes baseline and ANG II-induced superoxide generation equally in WT and gp91 phox -/- cardiomyocytes, suggesting gp91phox-independent mechanism of action. Baseline superoxide generation is higher in freshly-isolated adult UCP3 -/- mouse cardiomyocytes, compared to WT; and, treatment of UCP3 -/- cardiomyocytes with STC1 failed to suppress superoxide generation in the presence or absence of ANG II, suggesting that the effects of STC1 on superoxide generation are UCP3-mediated. Conclusion: STC1 activates a novel anti-oxidant pathway in cardiac myocytes through induction of UCP3; this pathway may play an important role in regulating reactive oxygen species in the heart under normal physiologic and pathophysiologic conditions, and ameliorate the deleterious effects of ANG II-mediated cardiac injury.
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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) | 0.001 | 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) | 0.004 | 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".