Antioxidant proteins in fetal brain: superoxide dismutase-1 (SOD-1) protein is not overexpressed in fetal Down syndrome

Exposure of living organisms to reactive oxygen species (ROS), notably oxyg en free radicals and hydrogen peroxide is closely linked to the very fact o f aerobic life. Oxidants, however, are not always detrimental for cell surv ival, indeed moderate concentrations of ROS serve as signaling molecules. T o maintain this level, cells have evolved an antioxidant defense system. Di sruption of this balance leads either to oxidative or reductive stress. Dow n syndrome (DS) is a genetic disorder associated with oxidative stress. Ove rexpression of superoxide dismutase-1 (SOD-1) as a result of gene loading i s suggested to be responsible for this phenomenon. To examine this view, we investigated the expression of thirteen different proteins involved in the cellular antioxidant defense system in brains of control and DS fetuses by two-dimensional electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization mass spectroscopy (MALDI-MS). No detectable change was found in expression of SOD-1, catalase, phospholip id hydroperoxide glutathione peroxidase, glutathione reductase, antioxidant enzyme AOE372, thioredoxin-like protein and selenium binding protein betwe en control and DS fetuses. By contrast, a significant reduction was observe d in levels of glutathione synthetase (P < 0.01), glutathione-S-transferase mu2 (P < 0.01), glutathione-S-transferase p (P < 0.05), antioxidant protei n 2 (P < 0.05), thioredoxin peroxidase-I (P < 0.05) and thioredoxin peroxid ase-II (P < 0.01) in DS compared with controls. The data suggest that oxida tive stress in fetal DS does not result from overexpression of SOD-1 protei n, rather oxidative stress appears to be the consequence of low levels of r educing agents and enzymes involved in removal of hydrogen peroxide.