PXD045233

PXD045233 is an original dataset announced via ProteomeXchange.

Title	α-Lipoic acid ameliorates consequences of copper overload by upregulating selenoproteins and decreasing redox misbalance
Description	α-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.
HostingRepository	PRIDE
AnnounceDate	2024-05-23
AnnouncementXML	Submission_2024-05-23_00:09:37.950.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Josh Smith
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-08 14:31:28	ID requested
⏵ 1	2024-05-23 00:09:38	announced

10.1073/pnas.2305961120;

submitter keyword: α-lipoic acid, selenoprotein,copper, Wilson disease, oxidative stress

Svetlana Lutsenko
contact affiliation	Johns Hopkins University
contact email	lutsenko@jhmi.edu
lab head
Josh Smith
contact affiliation	Johns Hopkins University
contact email	joshuasmith@jhu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045233
     1. Label: PRIDE project
     2. Name: α-Lipoic acid ameliorates consequences of copper overload by upregulating selenoproteins and decreasing redox misbalance