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PXD042070-2

PXD042070 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleClick Chemistry-based Thiol Redox Proteomics Reveals Significant Cysteine Reduction Induced by Chronic Ethanol Consumption
DescriptionIn 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:59:07.472.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD042070
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterCole Michel
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; deaminated residue; iodoacetamide derivatized residue
Instrument6550A iFunnel Q-TOF LC/MS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-05-08 19:09:35ID requested
12024-09-19 10:52:50announced
22024-10-22 06:59:07announced2024-10-22: Updated project metadata.
Publication List
10.1016/J.REDOX.2023.102792;
10.6019/PXD042070;
Keyword List
submitter keyword: Redox Proteomics, proteomics, glutathione, Mus musculus, Agilent 6550 Q-TOF, redox, Cysteine, thiol, click chemistry, alcohol-associated liver disease
Contact List
Kristofer Fritz
contact affiliationUniversity of Colorado Skaggs School of Pharmacy
contact emailKristofer.Fritz@Cuanschutz.edu
lab head
Cole Michel
contact affiliationUniveristy of Colorado - Skaggs School of Pharmacy
contact emailcole.michel@cuanschutz.edu
dataset submitter
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Dataset FTP location
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