Selenium supplementation protects trophoblast cells from oxidative stress.
Oxidative stress is a key feature in the pathogenesis of pre-eclampsia and antioxidants have been proposed as a potential therapy in the treatment of this important complication of pregnancy. In this report selenium supplementation was used to up-regulate the antioxidant enzymes glutathione peroxidase and thioredoxin reductase and the protective effect that this had on cellular metabolism during oxidative stress was examined. Bewo and Jeg-3 trophoblast cells were supplemented with organic and inorganic forms of selenium and 3 forms of peroxide in a range of doses were utilised to generate oxidative stress. Thioredoxin reductase and glutathione peroxidase activity were maximally expressed after supplementation with 100 nM NaSe and 500 nM SeMethionine. Application of H₂O₂ in the range of 200-400 μM for 24h resulted in significant (p<0.001) inhibition of cellular activity, an effect negated by Se supplementation. Tert-butyl H₂O₂ and cumene H₂O₂ concentrations between 30 and 50 uM similarly inhibited cellular activity and this could be significantly (p<0.001) reversed by Se supplementation. Auranofin, a specific inhibitor of thioredoxin reductase and glutathione peroxidase was used to prove that the protective effect generated by Se supplementation was due to up regulation of these enzymes. These studies provide direct evidence that selenium supplementation can up-regulate endogenous antioxidant systems and protects trophoblast cells from oxidative stress. This may inform the development of future therapies for pre-eclampsia and emphasises the importance of selenium adequacy during pregnancy.
School of Medical Science, Griffith Health Institute, Griffith University, Gold Coast Campus, Parklands Drive, Southport, QLD 9726, Australia.
M
M
Watson
L
L
van Leer
J J
JJ
Vanderlelie
A V
AV
Perkins
D001310:Auranofin / Q000494:pharmacology; D002460:Cell Line; D019587:Dietary Supplements; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009994:Osmolar Concentration; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D011225:Pre-Eclampsia / Q000517:prevention & control; D011247:Pregnancy; D020011:Protective Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D012643:Selenium / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D012645:Selenomethionine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D018038:Sodium Selenite / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D054481:Thioredoxin Reductase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054482:Thioredoxin Reductase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*; D000094765:Glutathione Peroxidase GPX1
D004791:Enzyme Inhibitors; D016877:Oxidants; D020011:Protective Agents; D001310:Auranofin; D012645:Selenomethionine; D005979:Glutathione Peroxidase; C516124:TXNRD1 protein, human; C516127:TXNRD2 protein, human; D054481:Thioredoxin Reductase 1; D054482:Thioredoxin Reductase 2; D012643:Selenium; D018038:Sodium Selenite; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human