PXD036300-3

PXD036300 is an original dataset announced via ProteomeXchange.

Title	Copper impairs hepatic selenoprotein P release
Description	Selenoprotein P is a hepatokine which is essential for maintaining systemic selenium homeostasis and is used as serum biomarker for the selenium status in humans. In addition to selenium, also copper homeostasis is mainly regulated by the liver coordinating systemic distribution of copper bound to ceruloplasmin or excreting surplus copper into the bile. Circulating selenium and copper concentrations are most often negatively correlating, e.g. during aging copper levels are increasing while selenium levels are decreasing. Based on these results, we addressed the question of how both trace elements interfere with each other using the liver-derived cell line HepG2. We observed that copper treatment resulted in a substantial increase of intracellular selenium concentrations. In parallel, extracellular SELENOP concentrations were drastically reduced while SELENOP accumulated within the cells. The same observation was made when using primary murine hepatocytes. Indeed, SELENOP was one of the proteins most strongly downregulated by copper in an untargeted secretome approach. Accumulation of hepatic copper is a characteristic of Wilson’s disease. Accordingly, SELENOP levels were decreasing in the serum of LPP rats, a model of Wilson’s disease starting at disease onset. Also, Wilson’s disease patients showed reduced serum SELENOP concentrations when circulating copper concentrations were low. This positive correlation between copper and ceruloplasmin and SELENOP was also observed in a GWAS analysis of EPIC-Potsdam samples identifying SNP rs11708215 as a modulating factor. Our data indicate that under conditions of a suboptimal selenium supply combined with a high copper intake a functional selenium deficit can become even worse because peripheral tissues such as the brain depend on SELENOP for their selenium supply.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:54:51.544.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anetta Hartlova
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; acetylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-25 14:56:07	ID requested
1	2023-07-20 10:46:04	announced
2	2023-11-14 09:02:45	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 05:54:52	announced	2024-10-22: Updated project metadata.

Schwarz M, Meyer CE, L, ö, ser A, Lossow K, Hackler J, Ott C, J, ä, ger S, Mohr I, Eklund EA, Patel AAH, Gul N, Alvarez S, Altinonder I, Wiel C, Maares M, Haase H, H, ä, rtlova A, Grune T, Schulze MB, Schwerdtle T, Merle U, Zischka H, Sayin VI, Schomburg L, Kipp AP, Excessive copper impairs intrahepatocyte trafficking and secretion of selenoprotein P. Nat Commun, 14(1):3479(2023) [pubmed]

10.1038/s41467-023-39245-3;

submitter keyword: selenoprotein P, Wilson’s disease,Selenium, copper, secretome

Anetta Härtlova
contact affiliation	Institute of Biomedicine, Department of Microbiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
contact email	anetta.hartlova@gu.se
lab head
Anetta Hartlova
contact affiliation	University of Gothenburg, Institute of Biomedicine, Dept. of Microbiology and Immunology
contact email	anetta.hartlova@gu.se
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/07/PXD036300

PRIDE project URI

• PRIDE
  1. PXD036300
     1. Label: PRIDE project
     2. Name: Copper impairs hepatic selenoprotein P release