Enhanced protein levels of protein thiol/disulphide oxidoreductases in placentae from pre-eclamptic subjects

Recent studies have indicated that pre-eclampsia is closely associated with oxidative stress both in maternal circulation and in the placenta. Protein thiol/disulphide oxidoreductases, such as thioredoxin, glutaredoxin, and p rotein disulphide isomerase have recently been found to eliminate reactive oxygen species (ROS) and regenerate oxidatively damaged proteins. Protein t hiol/disulphide oxidoreductases ma!; also play; a role in combating pre-ecl ampsia. In this study, we examined the accumulation of 4-hydroxy-2-nonenal (HNE)-modified proteins, which are markers of lipid peroxidation, in human placentae of normal and pre-eclamptic subjects. We also examined the protei n levels of thioredoxin, glutaredoxin, and protein disulphide isomerase in placentae. Immunoblotting and immunohistochemistry showed that HNE-modified proteins accumulated to a greater extent in pre-eclamptic placentae than i n normal placentae. In both normal and pre-eclamptic placentae, thioredoxin , glutaredoxin, and protein disulphide isomerase sere detected in the troph oblasts of the floating villi. The levels of these proteins were increased approximately; 2- to 3-fold in the pre-eclamptic placentae compared to the normal placentae. These results indicated that the pre-eclamptic placentae were exposed to oxidative stress and that the protein thiol/disulphide oxid oreductases were adaptively induced in pre-eclamptic placentae, suggesting possible roles for thioredoxin, glutaredoxin, and protein disulphide isomer ase in protecting placental functions against oxidative stress caused by pr e-eclampsia. (C) 2001 Harcourt Publishers Ltd.