Excessive copper impairs intrahepatocyte trafficking and secretion of selenoprotein P

Maria Schwarz, Caroline E. Meyer, Alina Löser, Kristina Lossow, Julian Hackler, Christiane Ott, Susanne Jäger, Isabelle Mohr, Ella A. Eklund, Angana A. H. Patel, Nadia Gul, Samantha Alvarez, Ilayda Altinonder, Clotilde Wiel, Maria Maares, Hajo Haase, Anetta Härtlova, Tilman Grune, Matthias B. Schulze, Tanja Schwerdtle, Uta Merle, Hans Zischka, Volkan I. Sayin, Lutz Schomburg and Anna P. Kipp ()
Additional contact information
Maria Schwarz: Friedrich Schiller University Jena
Caroline E. Meyer: Friedrich Schiller University Jena
Alina Löser: Friedrich Schiller University Jena
Kristina Lossow: Friedrich Schiller University Jena
Julian Hackler: TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly
Christiane Ott: TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly
Susanne Jäger: TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly
Isabelle Mohr: University Hospital Heidelberg
Ella A. Eklund: University of Gothenburg
Angana A. H. Patel: University of Gothenburg
Nadia Gul: University of Gothenburg
Samantha Alvarez: University of Gothenburg
Ilayda Altinonder: University of Gothenburg
Clotilde Wiel: University of Gothenburg
Maria Maares: TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly
Hajo Haase: TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly
Anetta Härtlova: University of Gothenburg
Tilman Grune: TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly
Matthias B. Schulze: TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly
Tanja Schwerdtle: TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly
Uta Merle: University Hospital Heidelberg
Hans Zischka: Technical University Munich, School of Medicine
Volkan I. Sayin: University of Gothenburg
Lutz Schomburg: TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly
Anna P. Kipp: Friedrich Schiller University Jena

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract 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.

Date: 2023
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-39245-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39245-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-39245-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().