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Excessive copper impairs intrahepatocyte trafficking and secretion of selenoprotein P.

Schwarz, Maria (author)
Meyer, Caroline E (author)
Löser, Alina (author)
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Lossow, Kristina (author)
Hackler, Julian (author)
Ott, Christiane (author)
Jäger, Susanne (author)
Mohr, Isabelle (author)
Eklund, Ella A (author)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Sahlgrenska Centrum för Cancerforskning (SCCR),Wallenberg Centre for Molecular and Translational Medicine,Institute of Clinical Sciences, Department of Surgery,Sahlgrenska Center for Cancer Research (SCCR)
Patel, Angana A. H. (author)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Wallenberg Centre for Molecular and Translational Medicine,Sahlgrenska Centrum för Cancerforskning (SCCR),Institute of Clinical Sciences, Department of Surgery,Sahlgrenska Center for Cancer Research (SCCR)
Gul, Nadia, 1980 (author)
Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Sahlgrenska Centrum för Cancerforskning (SCCR),Sahlgrenska Center for Cancer Research (SCCR)
Alvarez, Samantha (author)
Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Sahlgrenska Centrum för Cancerforskning (SCCR),Sahlgrenska Center for Cancer Research (SCCR)
Altinonder, Ilayda, 1996 (author)
Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery
Wiel, Clotilde, 1987 (author)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Wallenberg Centre for Molecular and Translational Medicine,Sahlgrenska Centrum för Cancerforskning (SCCR),Institute of Clinical Sciences, Department of Surgery,Sahlgrenska Center for Cancer Research (SCCR)
Maares, Maria (author)
Haase, Hajo (author)
Härtlova, Anetta (author)
Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Wallenberg Centre for Molecular and Translational Medicine,Institute of Biomedicine, Department of Microbiology and Immunology
Grune, Tilman (author)
Schulze, Matthias B (author)
Schwerdtle, Tanja (author)
Merle, Uta (author)
Zischka, Hans (author)
Sayin, Volkan I., 1983 (author)
Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Wallenberg Centre for Molecular and Translational Medicine,Sahlgrenska Center for Cancer Research (SCCR),Institute of Clinical Sciences, Department of Surgery
Schomburg, Lutz (author)
Kipp, Anna P (author)
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 (creator_code:org_t)
2023
2023
English.
In: Nature communications. - 2041-1723. ; 14:1
Related links:
https://gup.ub.gu.se...
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

Animals
Rats
Selenoprotein P
Hepatolenticular Degeneration
Selenium
Copper

Publication and Content Type

ref (subject category)
art (subject category)

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