Sulfhydrated albumin transmits H2S signaling and ameliorates DOX-induced multiorgan injuries
Bibliographic record
Abstract
Hydrogen sulfide (H 2 S) is a vital signaling molecule involved in various physiological processes; however, the mechanisms underlying its systemic signaling remain poorly understood. We hypothesized that albumin, the predominant plasma protein and a vital sulfhydryl carrier, mediated systemic H 2 S signaling, which could potentially treat H 2 S-deficient diseases. This study aimed to investigate this hypothesis. Our results showed the presence of sulfhydrated proteins in normal mouse serum, with albumin being particularly enriched. The level of sulfhydration was influenced by H 2 S availability and the redox environment. In vitro incubation of albumin with NaHS resulted in an increased number of sulfhydrated groups. Under reductive conditions, this sulfhydrated albumin (–SSH–Alb) released substantial amounts of H 2 S. When –SSH–Alb was added to cultured endothelial cells, it activated the cAMP signaling pathway, upregulated cystathionine γ-lyase (CSE) expression, and enhanced intracellular H 2 S levels. In an in vitro inflammatory model involving macrophages and endothelial cells, –SSH–Alb inhibited macrophage adhesion, reduced LPS-induced expression of adhesion molecules, and suppressed cytokine production and inflammasome activation. These effects correlated with improved cellular redox status. Furthermore, in vivo administration of –SSH–Alb protected mice from doxorubicin (DOX)-induced cardiotoxicity and intestinal damage. It improved mouse mortality, and alleviated ferroptotic cardiac injury and gut barrier dysfunction. These therapeutic benefits were associated with rebalanced local and systemic redox status. In summary, our study reveals that –SSH–Alb reserves, transmits, and amplifies H 2 S signals and exhibits significant anti-inflammatory and antioxidant properties. This characteristic of –SSH–Alb holds promise for preventing and treating a wide range of diseases. • Albumin is a major carrier of protein sulfhydration in blood serum. • Sulfhydrated albumin (–SSH–Alb) reserves, transmits and amplifies H 2 S signaling. • -SSH-Alb activates cAMP pathway and stimulates CSE expression. • -SSH-Alb exhibits potent anti-inflammatory and antioxidant effects. • -SSH-Alb protects against DOX-induced cardiotoxicity and intestinal injury in mice.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 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".