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Schwarz, M.* ; Meyer, C.E.* ; Löser, A.* ; Lossow, K.* ; Hackler, J.* ; Ott, C.* ; Jager, S.* ; Mohr, I.* ; Eklund, E.A.* ; Patel, A.A.H.* ; Gul, N.* ; Alvarez, S.* ; Altinonder, I.* ; Wiel, C.* ; Maares, M.* ; Haase, H.* ; Härtlova, A.* ; Grune, T.* ; Schulze, M.B.* ; Schwerdtle, T.* ; Merle, U.* ; Zischka, H. ; Sayin, V.I.* ; Schomburg, L.* ; Kipp, A.P.*

Excessive copper impairs intrahepatocyte trafficking and secretion of selenoprotein P.

Nat. Commun. 14:3479 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Selenium homeostasis depends on hepatic biosynthesis of selenoprotein P (SELENOP) and SELENOP-mediated transport from the liver to e.g. the brain. In addition, the liver maintains copper homeostasis. Selenium and copper metabolism are inversely regulated, as increasing copper and decreasing selenium levels are observed in blood during aging and inflammation. Here we show that copper treatment increased intracellular selenium and SELENOP in hepatocytes and decreased extracellular SELENOP levels. Hepatic accumulation of copper is a characteristic of Wilson’s disease. Accordingly, SELENOP levels were low in serum of Wilson’s disease patients and Wilson’s rats. Mechanistically, drugs targeting protein transport in the Golgi complex mimicked some of the effects observed, indicating a disrupting effect of excessive copper on intracellular SELENOP transport resulting in its accumulation in the late Golgi. Our data suggest that hepatic copper levels determine SELENOP release from the liver and may affect selenium transport to peripheral organs such as the brain.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Golgi-complex; Selenium; Quantification; Glycosylation; Metabolism; Expression; Transport; Proteins; Kidney; Model
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 14, Issue: 1, Pages: , Article Number: 3479 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOXI)
Grants Formas
Swedish Research Council
Swedish Society for Medical Research
Carl Zeiss Foundation
German Research Foundation (DFG)