Molecular characterization of selenoproteins based on decreased glutathione peroxidase activity in preeclampsia

Abstract

Glutathione peroxidase (GPx) and other selenoproteins (SeP) are involved in the detoxification of reactive oxygen species (ROS). ROS is implicated in preeclampsia (PE). Generation of ROS and antioxidant effect of total GPx in women with PE was estimated. Since we found a significant decrease in total GPx level of women with PE, we were motivated to characterize at a molecular level SeP present in GPx (GPx 1–4, 6). Other SeP including selenoprotein P (SEPP), selenoprotein S (SELS) and thioredoxin reductase (TXNRD) were also analyzed since literature suggests that they also play a critical role in down regulation of oxidative stress (OS) in PE. Non SeP GPx were also analyzed for comparison purposes. Serum GPx was measured in venous blood samples of women with PE (Group A; n=25) and normotensive pregnant women (Group B; n=32) spectrophotometrically. Intracellular ROS generated by peripheral blood mononuclear cells was measured using flow cytometry. Molecular characterization of the SeP was done by sequence analysis at nucleotide, codon and amino acid levels. Intracellular ROS level was significantly increased in Group A as compared to Group B. ROS and GPx were significantly negatively correlated in both Group A and Group B. SePs involved in PE, primarily belonged to two nucleotide biasing groups, AT and GC. Dinucleotide usage and codon preferences in these two groups were found to be in accordance with their respective compositional bias. Such nucleotide compositional bias seemed to be major factor driving their selective codon choices. These SePs differ within themselves with respect to their relative amino acid abundance.