Selenoprotein P protects endothelial cells from oxidative damage by stimulation of glutathione peroxidase expression and activity.
A major fraction of the essential trace element selenium circulating in human blood plasma is present as selenoprotein P (SeP). As SeP associates with endothelial membranes, the participation of SeP in selenium-mediated protection against oxidative damage was investigated, using the human endothelial cell line Ea.hy926 as a model system. Hepatocyte-derived SeP prevented tert-butylhydroperoxide (t-BHP)-induced oxidative cell death of Ea.hy926 cells in a similar manner as did sodium selenite, counteracting a t-BHP-induced loss of cellular membrane integrity. Protection was detected after at least 10 h of SeP supplementation and it peaked at 24 h. SeP time-dependently stimulated the expression of cytosolic glutathione peroxidase (cGPx) and increased the enzymatic activities of glutathione peroxidase (GPx) and thioredoxin reductase (TR). The cGPx inhibitor mercaptosuccinate as well as the gamma-glutamylcysteine synthetase inhibitor buthionine sulfoximine counteracted the SeP-mediated protection, while the TR inhibitors cisplatin and auranofin had no effect. The presented data suggest that selenium supplementation by SeP prevents oxidative damage of human endothelial cells by restoring expression and enzymatic activity of GPx.
Steinbrenner
Holger
H
Institute for Biochemistry and Molecular Biology I, Heinrich-Heine-University, Universitaetsstrasse 1, 40225, Duesseldorf, Germany.
Bilgic
Esra
E
Alili
Lirija
L
Sies
Helmut
H
Brenneisen
Peter
P
D019328:Buthionine Sulfoximine / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D051149:Selenoprotein P / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013386:Succinates / Q000494:pharmacology; D013880:Thioredoxin-Disulfide Reductase / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D051149:Selenoprotein P; D013386:Succinates; D019328:Buthionine Sulfoximine; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase