title: Selenium supplementation acting through the induction of thioredoxin reductase and glutathione peroxidase protects the human endothelial cell line EAhy926 from damage by lipid hydroperoxides.
abstract: The human endothelial cell line EAhy926 was used to determine the importance of selenium in preventing oxidative damage induced by tert-butyl hydroperoxide (tert-BuOOH) or oxidised low density lipoprotein (LDLox). In cells grown in a low selenium medium, tert-BuOOH and LDLox killed cells in a dose-dependent manner. At 555 mg/l LDLox or 300 microM tert-BuOOH, >80% of cells were killed after 20 h. No significant cell kill was achieved by these agents if cells were pre-incubated for 48 h with 40 nM sodium selenite, a concentration that maximally induced the activities of cytoplasmic glutathione peroxidase (cyGPX; 5.1-fold), phospholipid hydroperoxide glutathione peroxidase (PHGPX;1.9-fold) and thioredoxin reductase (TR; 3.1-fold). Selenium-deficient cells pre-treated with 1 microM gold thioglucose (GTG) (a concentration that inhibited 25% of TR activity but had no inhibitory effect on cyGPX or PHGPX activity) were significantly (P<0.05) more susceptible to tert-BuOOH toxicity (LC(50) 110 microM) than selenium-deficient cells (LC(50) 175 microM). This was also the case for LDLox. In contrast, cells pre-treated with 40 nM selenite prior to exposure to GTG were significantly more resistant to damage from tert-BuOOH and LDLox than Se-deficient cells. Treatment with GTG or selenite had no significant effect on intracellular total glutathione concentrations. These results suggest that selenium supplementation, acting through induction of TR and GPX, has the potential to protect the human endothelium from oxidative damage.
authors.affiliation: University Department of Clinical Biochemistry, The Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK.
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Lewin
authors.forename: John R
authors.initials: JR
authors.lastname: Arthur
authors.forename: Rudolph A
authors.initials: RA
authors.lastname: Riemersma
authors.forename: Fergus
authors.initials: F
authors.lastname: Nicol
authors.forename: Simon W
authors.initials: SW
authors.lastname: Walker
authors.forename: E Margaret
authors.initials: EM
authors.lastname: Millar
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Howie
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Beckett
mesh_terms: D006051:Aurothioglucose / Q000008:administration & dosage / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D004790:Enzyme Induction / Q000502:physiology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000096:biosynthesis*; D006801:Humans; D008054:Lipid Peroxides / Q000009:adverse effects / Q000378:metabolism*; D018038:Sodium Selenite / Q000008:administration & dosage / Q000378:metabolism*; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D020122:tert-Butylhydroperoxide / Q000009:adverse effects / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D008054:Lipid Peroxides; D006051:Aurothioglucose; D020122:tert-Butylhydroperoxide; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase; D018038:Sodium Selenite