S-Sulfhydration of SIRT3 by Hydrogen Sulfide Attenuates Mitochondrial Dysfunction in Cisplatin-Induced Acute Kidney Injury
Why this work is in the frame
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Bibliographic record
Abstract
Aims: Clinical use of cisplatin (Cisp), one of the most widely used, common, and effective chemotherapeutic agents, is limited by its side effects, particularly tubular injury-associated nephrotoxicity. Previous studies suggest that hydrogen sulfide (H 2 S) alleviates Cisp-induced acute kidney injury (AKI). However, the underlying mechanism remains largely unclear. Results: A single intraperitoneal injection of Cisp is employed to induce AKI, and the mice exhibit severe kidney dysfunction and histological damage at day 4 after Cisp injection. Here, we reported that H 2 S alleviated Cisp-caused renal toxicity via SIRT3 activation and subsequent improvement of mitochondrial ATP production. Using a biotin-switch assay, we showed that H 2 S increased S-sulfhydration of SIRT3 and induced deacetylation of its target proteins (OPA1, ATP synthase β, and superoxide dismutase 2). These effects of H 2 S were associated with a reduction of mitochondrial fragmentation, an increase in ATP generation, and less oxidative injury. Notably, the S-sulfhydration of SIRT3 induced by H 2 S was abrogated when Cys256, Cys259, Cys280, and Cys283 residues on SIRT3 (two zinc finger domains) were mutated. Innovation and Conclusion: Our data suggest that H 2 S attenuates Cisp-induced AKI by preventing mitochondrial dysfunction via SIRT3 sulfhydrylation. Antioxid. Redox Signal. 31, 1302–1319.
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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 it