Hydrogen sulfide modulates basal metabolic circuitry A transcriptome sequencing assisted insight
Bibliographic record
Abstract
Hydrogen Sulfide (H2S), the third gasomessenger to be discovered after nitric oxide (NO) and carbon monoxide (CO), is known for its distinctive health promoting effects on various organ systems, including cardiovascular system. This molecule has now qualified as an authentic mediator of specific cellular signal transduction pathways [1, 2]. The mechanistic insight into its cyto-protective role however remains incompletely understood. To understand the molecular circuitry regulated by H2S augmentation, we utilized an exogenous donor of H2S, Sodium hydrogen sulfide (NaHS), and performed unbiased global transcriptome sequencing (Illumina) in cardiac cells (H9c2 cardiomyoblasts). These experiments yielded differential transcriptome of the cells with varying levels of H2S (with or without NaHS treatment for 6 hrs). We subjected this dataset to multiple pathway mining tools, including gene ontology analysis, functional annotation clustering and co-expression network analysis, to infer biological themes hidden as concerted differential gene expression signatures [3]. We, interestingly, observed common biological processes in different analysis strategies, suggesting authentic, conserved nature of cellular response to H2S. Biological networks, largely associated with metabolic/ redox processes were recognized; within three gross themes - steroid/ isoprenoid biosynthesis, oxidoreductase coenzyme metabolism (representing pentose phosphate pathway, PPP) and glutathione metabolism. Glucose-6- phosphate dehydrogenase (G6PD) - rate-limiting enzyme within PPP stood as the highest degree node in majority of these networks. Also, genes related to oxidative stress and redox signaling were enriched. Interestingly, these pathways appear to be centrally linked by nicotinamide nucleotide cofactor (NADPH) homeostasis. We further supported this proposition at functional level by performing various enzyme activities besides recording cellular NADP/NADPH and GSH levels in established cellular as well as rat model system. In summary, our data suggested profound influence of H2S on integrated cellular metabolic circuitry modulating redox homeostasis in cardiac cells.
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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 | 0.001 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".