ArticleScience advances2016
A novel persulfide detection method reveals protein persulfide- and polysulfide-reducing functions of thioredoxin and glutathione systems.
Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
176 citing papers in PubMed, 317 citations in OpenAlex.
- Sulfide dynamics at the gut-microbiota interface: diet, oxygen and redox interplay.Gut microbes · 2026Review
- Protein thiol alterations drive pathologic liquid-liquid phase separation in the aging brain.Nature structural & molecular biology · 2026Article
- Hydrogen sulfide-mediated protein s-persulfidation: a regulatory mechanism in cardiovascular homeostasis.Molecular medicine (Cambridge, Mass.) · 2026Review
- Endogenous Sulfane Sulfur Mediates the Oxidative Stress Response Process inAntioxidants (Basel, Switzerland) · 2026Article
- Cystine C-S bond cleavage fuels cysteine production under disulfide reductase deficiency.Nature chemical biology · 2026Article
- Formation of a reducing microenvironment and regulation of protein supersulfidation by gut microbial supersulfides.Redox biology · 2026Article
- Multifaceted roles for persulfide species in redox chemical biology.Nature chemical biology · 2026Review
- The Role of Ferroptosis in Diabetes Pathogenesis: Therapeutic Implications of Hydrogen Sulfide and Its Reactive Metabolites.Antioxidants (Basel, Switzerland) · 2026Review
- Cystathionine γ-lyase is a major regulator of cognitive function through neurotrophin signaling and neurogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Simultaneous and sensitive quantification of protein and low molecular weight persulfides, polysulfides and HNature communications · 2025Article
- HAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Unique response of polysulfide in serum albumin to oxidative stress.Scientific reports · 2025Article
- Article
- Sulfite oxidase deficiency causes persulfidation loss and hydrogen sulfide release.The Journal of clinical investigation · 2025Article
- HHorticulture research · 2025Article
- Profiling the landscape of cysteine posttranslational modifications in brain aging and neurodegeneration.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Reactive sulfur species mediated persulfidation cascade regulation mechanism of novel transcription factor SscRAc in extremophile Acidithiobacillus caldus under extreme copper stress.Nucleic acids research · 2025Article
- Benchmark for Quantitative Global and Redox Proteomics Analysis by Combining Protein-Aggregation Capture and Data Independent Acquisition.Analytical chemistry · 2025Article
- Reactive Sulfur Species and Protein Persulfidation: An Emerging Redox Axis in Human Health and Disease.Current issues in molecular biology · 2025Review
- Bicyclic Selenenyl Sulfides with Tuned Bioreductive Step Rates Reveal Constraints for Probes Targeting Thioredoxin Reductase.Angewandte Chemie (International ed. in English) · 2025Article
116 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
Hydrogen sulfide signaling involves persulfide formation at specific protein Cys residues. However, overcoming current methodological challenges in persulfide detection and elucidation of Cys regeneration mechanisms from persulfides are prerequisites for constructing a bona fide signaling model. We here establish a novel, highly specific protein persulfide detection protocol, ProPerDP, with which we quantify 1.52 ± 0.6 and 11.6 ± 6.9 μg/mg protein steady-state protein persulfide concentrations in human embryonic kidney 293 (HEK293) cells and mouse liver, respectively. Upon treatment with polysulfides, HEK293 and A549 cells exhibited increased protein persulfidation. Deletion of the sulfide-producing cystathionine-γ-lyase or cystathionine-β-synthase enzymes in yeast diminished protein persulfide levels, thereby corroborating their involvement in protein persulfidation processes. We here establish that thioredoxin (Trx) and glutathione (GSH) systems can independently catalyze reductions of inorganic polysulfides and protein persulfides. Increased endogenous persulfide levels and protein persulfidation following polysulfide treatment in thioredoxin reductase-1 (TrxR1) or thioredoxin-related protein of 14 kDa (TRP14) knockdown HEK293 cells indicated that these enzymes constitute a potent regeneration system of Cys residues from persulfides in a cellular context. Furthermore, TrxR1-deficient cells were less viable upon treatment with toxic amounts of polysulfides compared to control cells. Emphasizing the dominant role of cytosolic disulfide reduction systems in maintaining sulfane sulfur homeostasis in vivo, protein persulfide levels were markedly elevated in mouse livers where hepatocytes lack both TrxR1 and glutathione reductase (TR/GR-null). The different persulfide patterns observed in wild-type, GR-null, and TR/GR-null livers suggest distinct roles for the Trx and GSH systems in regulating subsets of protein persulfides and thereby fine-tuning sulfide signaling pathways.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.