PXD042070-2

PXD042070 is an original dataset announced via ProteomeXchange.

Title	Click Chemistry-based Thiol Redox Proteomics Reveals Significant Cysteine Reduction Induced by Chronic Ethanol Consumption
Description	In the U.S., alcohol-associated liver disease (ALD) impacts millions of people and is a major healthcare burden. While the pathology of ALD is unmistakable, the molecular mechanisms underlying ethanol hepatotoxicity are not fully understood. Hepatic ethanol metabolism is intimately linked with alterations in extracellular and intracellular metabolic processes, specifically oxidation/reduction reactions. The xenobiotic detoxification of ethanol leads to significant disruptions in glycolysis, β-oxidation, and the TCA cycle, as well as oxidative stress. Perturbation of these regulatory networks impacts the redox status of critical regulatory protein thiols throughout the cell. Integrating these key concepts, our goal was to apply a cutting-edge approach toward understanding mechanisms of ethanol metabolism in disrupting hepatic thiol redox signaling. Utilizing a chronic murine model of ALD, we applied a cysteine targeted click chemistry enrichment coupled with quantitative nHPLC-MS/MS to assess the thiol redox proteome. Our strategy reveals that ethanol metabolism largely reduces the cysteine proteome, with 593 cysteine residues significantly reduced and 8 significantly oxidized cysteines. Ingenuity Pathway Analysis demonstrates that ethanol metabolism reduces specific cysteines throughout ethanol metabolism (Adh1, Cat, Aldh2), antioxidant pathways (Prx1, Mgst1, Gsr), as well as many other biochemical pathways. Further research is needed to determine how a reduced cysteine proteome impacts individual protein activity across these protein targets and pathways. Additionally, understanding how a complex array of cysteine-targeted post-translational modifications (e.g., S-NO, S-GSH, S-OH) are integrated to regulate redox signaling and control throughout the cell is key to the development of redox-centric therapeutic agents targeted to ameliorate the progression of ALD.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:59:07.472.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD042070
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Cole Michel
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; deaminated residue; iodoacetamide derivatized residue
Instrument	6550A iFunnel Q-TOF LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-08 19:09:35	ID requested
1	2024-09-19 10:52:50	announced
⏵ 2	2024-10-22 06:59:07	announced	2024-10-22: Updated project metadata.

10.1016/J.REDOX.2023.102792;

10.6019/PXD042070;

submitter keyword: Redox Proteomics, proteomics, glutathione, Mus musculus, Agilent 6550 Q-TOF, redox, Cysteine, thiol, click chemistry, alcohol-associated liver disease

Kristofer Fritz
contact affiliation	University of Colorado Skaggs School of Pharmacy
contact email	Kristofer.Fritz@Cuanschutz.edu
lab head
Cole Michel
contact affiliation	Univeristy of Colorado - Skaggs School of Pharmacy
contact email	cole.michel@cuanschutz.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042070
     1. Label: PRIDE project
     2. Name: Click Chemistry-based Thiol Redox Proteomics Reveals Significant Cysteine Reduction Induced by Chronic Ethanol Consumption