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PXD045233

PXD045233 is an original dataset announced via ProteomeXchange.

Dataset Summary
Titleα-Lipoic acid ameliorates consequences of copper overload by upregulating selenoproteins and decreasing redox misbalance
Descriptionα-Lipoic acid (LA) is an essential cofactor for mitochondrial dehydrogenases and is required for cell growth, metabolic fuels production, and antioxidant defense. In vitro, LA binds copper (Cu) with high affinity, and as an endogenous membrane permeable metabolite could be advantageous in mitigating the consequences of Cu overload in human diseases. We tested this hypothesis in 3T3-L1 preadipocytes with inactivated Cu transporter Atp7a; these cells accumulate Cu and show morphologic changes and mitochondria impairment. Treatment with LA corrected the morphology of Atp7a-/- 60 cells similar to the Cu chelator bathocuproinedisulfonate (BCS) and improved mitochondria function; however, the mechanisms of LA and BCS action were different. Unlike BCS, LA did not decrease intracellular Cu, but instead increased selenium levels that were low in Atp7a-/- cells. Proteome analysis confirmed distinct cell responses to these compounds and identified upregulation of selenoproteins as the major effect of LA on preadipocytes. Upregulation of selenoproteins was associated with improved GSH:GSSG ratio in cellular compartments, which was lowered by elevated Cu, and reversal of protein oxidation. Thus, LA diminishes toxic effects of elevated Cu by improving cellular redox environment. We also show that selenium levels are decreased in tissues of Wilson disease animal model, especially in the liver, making LA an attractive candidate for supplemental treatment of this disease.
HostingRepositoryPRIDE
AnnounceDate2024-05-23
AnnouncementXMLSubmission_2024-05-23_00:09:37.950.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJosh Smith
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos; Orbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-09-08 14:31:28ID requested
12024-05-23 00:09:38announced
Publication List
Kabin E, Dong Y, Roy S, Smirnova J, Smith JW, Ralle M, Summers K, Yang H, Dev S, Wang Y, Devenney B, Cole RN, Palumaa P, Lutsenko S, -lipoic acid ameliorates consequences of copper overload by up-regulating selenoproteins and decreasing redox misbalance. Proc Natl Acad Sci U S A, 120(40):e2305961120(2023) [pubmed]
10.1073/pnas.2305961120;
Keyword List
submitter keyword: α-lipoic acid, selenoprotein,copper, Wilson disease, oxidative stress
Contact List
Svetlana Lutsenko
contact affiliationJohns Hopkins University
contact emaillutsenko@jhmi.edu
lab head
Josh Smith
contact affiliationJohns Hopkins University
contact emailjoshuasmith@jhu.edu
dataset submitter
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