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Holger Steinbrenner, Lirija Alili, Dominik Stuhlmann, Helmut Sies, Peter Brenneisen
Posttranslational processing of selenoprotein P: implications of glycosylation for its utilisation by target cells
Keywords: calcium, Ea.hy926 endothelial cell, glutathione peroxidase, monensin, selenium, tunicamycin
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 in order to examine posttranslational processing and secretion of selenoprotein P by HepG2 cells. In parallel, the prototypic secretory glycoprotein ?1-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 nonglycosylated and partially glycosylated forms of SeP, which were secreted in spite of their impaired glycosylation. Both nonglycosylated 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 (cGPx) nor its capacity to protect endothelial cells from oxidative stress.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 2007
Pages: -