title: Post-translational processing of selenoprotein P: implications of glycosylation for its utilisation by target cells.
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 alpha1-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.
authors.affiliation: Institute for Biochemistry and Molecular Biology I, Heinrich Heine University Düsseldorf, Universitätstrasse 1, D-40225 Düsseldorf, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Steinbrenner
authors.forename: Lirija
authors.initials: L
authors.lastname: Alili
authors.forename: Dominik
authors.initials: D
authors.lastname: Stuhlmann
authors.forename: Helmut
authors.initials: H
authors.lastname: Sies
authors.forename: Peter
authors.initials: P
authors.lastname: Brenneisen
mesh_terms: D002118:Calcium / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D011499:Protein Processing, Post-Translational; D012643:Selenium / Q000378:metabolism; D051149:Selenoprotein P / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051149:Selenoprotein P; D012643:Selenium; D002118:Calcium