Relationship between the critical level of oxidative stresses and the glutathione peroxidase activity.
The production and removal of the various oxygen-derived free radicals is a dynamic and complex process which normally results in a steady state of very low concentrations of these reactive molecules in the cell. The mathematical modelling of this process showed that any lowering of the glutathione peroxidase activity will increase the steady state level of the hydroperoxides and will decrease the level of organic peroxides necessary to destabilize the system. In this paper, we experimentally tested this relationship by the estimation of the level of peroxidative stresses which lead to cell degeneration in the presence of more or less active selenium-dependent glutathione peroxidase (GPX). The enzyme was inhibited by mercaptosuccinate (MS) and the cells were submitted to various extents of oxidative stress using tert-butylhydroperoxide (TBHP). Critical levels of this peroxidative molecule could be determined by the determination of the concentration leading to 50% cell death. A relationship between this critical level of TBHP and the GPX activity was established. The critical level strongly decreased with the inhibition of GPX and was found to be zero when 44% of the GPX activity is inhibited. Presented in this way, the results clearly show the pattern of the inverse relationship between the susceptibility of the cell to oxidative stress and the GPX activity.
Laboratoire de biochimie cellulaire, Facultés Universitaires N.-D. de la Paix, Namur, Belgium.
O
O
Toussaint
A
A
Houbion
J
J
Remacle
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005347:Fibroblasts / Q000378:metabolism; D005609:Free Radicals; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors*; D006801:Humans; D008962:Models, Theoretical; D010084:Oxidation-Reduction; D010545:Peroxides / Q000633:toxicity; D013870:Thiomalates / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D005609:Free Radicals; D010545:Peroxides; D013870:Thiomalates; C046062:2-thiomalic acid; D020122:tert-Butylhydroperoxide; D005979:Glutathione Peroxidase