Post-translational processing of selenoprotein P: implications of glycosylation for its utilisation by target cells

Holger Steinbrenner 1 , 1 , Lirija Alili 2 , 2 , Dominik Stuhlmann 3 , 3 , Helmut Sies 4 , 4  and Peter Brenneisen 5 , 5
  • 1 Institute for Biochemistry and Molecular Biology I, Heinrich Heine University Düsseldorf, Universitätstrasse 1, D-40225 Düsseldorf, Germany
  • 2 Institute for Biochemistry and Molecular Biology I, Heinrich Heine University Düsseldorf, Universitätstrasse 1, D-40225 Düsseldorf, Germany
  • 3 Institute for Biochemistry and Molecular Biology I, Heinrich Heine University Düsseldorf, Universitätstrasse 1, D-40225 Düsseldorf, Germany
  • 4 Institute for Biochemistry and Molecular Biology I, Heinrich Heine University Düsseldorf, Universitätstrasse 1, D-40225 Düsseldorf, Germany
  • 5 Institute for Biochemistry and Molecular Biology I, Heinrich Heine University Düsseldorf, Universitätstrasse 1, D-40225 Düsseldorf, Germany

Abstract

Selenoprotein P (SeP) is a highly glycosylated plasma protein containing up to 10 selenocysteine residues. It is secreted by hepatocytes and also by the human hepatoma cell line HepG2. Pharmacological inhibitors interfering with N-glycosylation, intracellular trafficking and calcium homeostasis were applied to examine post-translational processing and secretion of SeP by HepG2 cells. In parallel, the prototypic secretory glycoprotein α1-antitrypsin was used as technical control. Secretion of SeP was stimulated by increasing the extracellular calcium concentration and by inhibiting the release of sequestered calcium through dantrolene or U-73122. In contrast, brefeldin A and thapsigargin suppressed SeP secretion. Tunicamycin and monensin induced the synthesis of truncated non-glycosylated and partially glycosylated forms of SeP, which were secreted in spite of their impaired glycosylation. Both non-glycosylated and partially glycosylated SeP is utilised as selenium donor by target cells: impaired glycosylation affected neither the ability of SeP to induce the synthesis of the selenoenzyme cytosolic glutathione peroxidase nor its capacity to protect endothelial cells from oxidative stress.

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Biological Chemistry keeps you up-to-date with the latest advances in the molecular life sciences. The journal publishes Research Articles, Short Communications, Reviews and Minireviews. Areas include: general biochemistry/pathobiochemistry, structural biology, molecular and cellular biology, genetics and epigenetics, virology, molecular medicine, plant molecular biology/biochemistry and novel experimental methodologies.

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