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Lower H2S-generating enzyme levels and persulfidation-mediated protein protection characterize metabolic dysfunction-associated steatohepatitis

ABSTRACT: Metabolic dysfunction–associated steatohepatitis (MASH), marked by hepatic steatosis and inflammation, is a major risk for cirrhosis and liver cancer. Obesity-induced oxidative stress plays a central role in MASH promoting protein damage and dysfunction. Cysteine persulfidation (PSSH), a post-translational modification regulated by hydrogen sulfide (H2S), is involved in protein stability and cellular protection. However, the role of PSSH in MASH is poorly understood. We found that H2S-producing enzymes are downregulated in livers with fibrosis and inflammation, leading to decreased hepatic PSSH. Using dimedone-switch-based mass spectrometry, we mapped the alterations in the liver persulfidome during diet-induced fibrosis and inflammation. While the levels of H2S-producing enzymes dropped, some proteins, including protein tyrosine phosphatases (PTPs) and redox regulators, showed increased PSSH. This change suggests that H2S-mediated persulfidation helps protect proteins from oxidative damage. Overall, decreased H2S enzyme expression and reduced PSSH may impair protection against oxidative stress, contributing to liver dysfunction in obesity.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

DISEASE(S): Metabolic Dysfunction-associated Steatotic Liver Disease

SUBMITTER: Elisavet Kalaitsidou

LAB HEAD: Wei Wu

PROVIDER: PXD057932 | Pride | 2025-08-04

REPOSITORIES: Pride

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			Action	DRS
	20210827_EX2_UM1_wu000024_SA_EXT00_PTP5_proteomeD1.raw	Raw
	20210827_EX2_UM1_wu000024_SA_EXT00_PTP5_proteomeD10.raw	Raw
	20210827_EX2_UM1_wu000024_SA_EXT00_PTP5_proteomeD11.raw	Raw
	20210827_EX2_UM1_wu000024_SA_EXT00_PTP5_proteomeD12.raw	Raw
	20210827_EX2_UM1_wu000024_SA_EXT00_PTP5_proteomeD13.raw	Raw

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