Dataset Information

Pathology-driven epithelial sulfide loss reprograms the redox proteome and triggers Barrett’s esophagus

ABSTRACT: Background & AimsBarrett’s esophagus (BE), a metaplastic transformation driven by gastroesophageal reflux disease (GERD), induces oxidative stress but the underlying redox mechanisms remain poorly understood. Protein persulfidation (PSSH), a redox-sensitive, reversible, and antioxidative post-translational modification regulated by hydrogen sulfide (H₂S) metabolism, has not been explored in this context. Here, we identify epithelial PSSH as a key regulator of this premalignant process.MethodsWe applied proteomics and chemoproteomics in patients to map and validate PSSH and total proteome profiles across healthy (squamous), GERD-exposed, and metaplastic epithelium. Using in vitro and in vivo models of chronic GERD and BE, we modulated H₂S levels genetically and pharmacologically. Mechanistic and functional effects were assessed using tissue biopsies or recombinant human proteins.ResultsGERD-induced oxidative loss of H₂S and its enhanced catabolism initiated early PSSH proteome remodeling in squamous epithelium, which expanded in BE and affected >1,300 proteins in clinical samples, indicating potential biomarkers. This also included altered persulfidation of enzymes regulating the accumulation of prostaglandin E₂ (PGE₂), a well-established driver of BE development and progression. H₂S depletion accelerated metaplastic transformation, whereas H₂S donors reversed these effects in experimental models. PSSH of 15-hydroxyprostaglandin dehydrogenase (PGDH) reversibly suppressed its activity, protecting the enzyme and, unlike irreversible oxidation, allowing recovery of PGE₂ degradation.ConclusionsThese findings redefine the origin of PGE₂ accumulation in metaplasia and establish sulfide loss and persulfidomic remodeling as central, druggable drivers of epithelial reprogramming and redox imbalance in BE pathogenesis.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Esophagus

DISEASE(S): Barrett's Esophagus

SUBMITTER: Thibaut Vignane

LAB HEAD: Milos Filipovic

PROVIDER: PXD047338 | Pride | 2026-06-02

REPOSITORIES: pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 63

Similar Datasets

Project description:Hydrogen sulfide is an important signaling molecule in plants that regulates essential biological processes through protein persulfidation. Although numerous persulfidated proteins were found to be involved in photorespiration, little was known about sulfide-mediated regulation of photorespiration. Label-free quantitative proteomic analysis has revealed a high impact on the protein persulfidation level when plants grown under non-photorespiratory conditions are transferred to air, with the 97 % of total identified proteins more persulfidated under suppressed photorespiration. A detailed study of the effect of sulfide on important aspects associated with photorespiratory growth conditions has provided insight into the role of sulfide in protecting plants grown under suppressed photorespiration. In these conditions, sulfide amends the metabolic imbalance of carbon/nitrogen and restores ATP levels to concentrations similar to those in air grown conditions. Sulfide also plays an essential role in balancing the significant high level of ROS measured in plants under non-photorespiratory conditions to reach a similar cellular redox state in air-grown plants, through the regulation of antioxidative defenses. Furthermore, sulfide regulates another important characteristic resulting from suppression of photorespiration, such as the stomata closure, to decrease the high guard cell ROS levels and inducing the stomata aperture. In this way, sulfide signals the movement of the CO2-dependent stomata to achieve a scenario similar to that of plants growing under normal air conditions, in the opposite direction of the already established ABA-dependent movement of the stomata. Therefore, our findings suggest that the high persulfidation level under suppressed photorespiration reveals an essential role of sulfide signaling under these conditions, and with respect to stomatal movement, the outcome of this signaling is dependent on the growth/stress condition under study.

Project description:Hydrogen sulfide (H2S) is a signaling molecule that regulates essential plant processes, such as autophagy and responses to abiotic stresses. Although there is much information about the processes in which H2S is involved, the mechanism of action of H2S is still unclear. However, the posttranslational modification of cysteine residues, named persulfidation, is the main proposed mechanism. In this study, the role of H2S during drought that allows plant stress adaptation has been analyzed, with the focus on the underlying mechanism. H2S pretreatment before imposing drought on plants significantly improved phenotypic traits and decreased the content of biochemical and molecular drought stress markers. In addition, H2S regulated amino acid metabolism and repressed drought-induced degradation pathways, such as bulk autophagy and protein ubiquitination. The label-free quantitative proteomic analysis of plants growing under control and drought stress identified 887 proteins significantly different persulfidated between both conditions. Bioinformatic analyses revealed that the biological processes most enriched containing the proteins more persulfidated in drought corresponded to cellular response to oxidative stress, and hydrogen peroxide catabolism. In addition, protein degradation, abiotic stress responses, anthocyanin-containing compound biosynthetic process, and flavonoid biosynthesis were highlighted. On the contrary, the most enriched biological process containing proteins with lower levels of persulfidation in drought corresponded to the biosynthetic processes of glucosinolates and chlorophyll. Therefore, our findings emphasize the role of H2S as a promoter of enhanced tolerance to drought, enabling plants to respond more rapidly and efficiently after exposure to drought. Furthermore, the proteomic analysis supports the main role of protein persulfidation as the molecular mechanism of H2S to alleviate ROS accumulation and balance redox homeostasis under drought stress.

			Action	DRS
	FPdb.mzidentml.xml.gz	Mzid
	PSSH_results.xlsx	Xlsx
	PSSHdb.mzidentml.xml.gz	Mzid
	SDRF_Totalproteome.tsv	Tabular
	SDRF_persulfidation.tsv	Tabular

Dataset Information

Pathology-driven epithelial sulfide loss reprograms the redox proteome and triggers Barrett’s esophagus

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets