Specific systemic antioxidant response to preeclampsia in late pregnancy: the study of intracellular glutathione peroxidases in maternal and fetal blood.
OBJECTIVE
The physiopathology of preeclampsia is still unclear, but an imbalance between reactive oxygen species (ROS) and antioxidants, also called oxidative stress, appears to be an important contributing factor. The ROS promote lipid oxidation and are known to induce stress proteins, such as hemeoxygenase 1 (HO-1) and heat-shock protein 70 (Hsp-70). We hypothesized that glutathione peroxidases (GPx), a major class of antioxidant enzymes that regulate cell homeostasis by neutralizing lipid peroxides, are altered in the blood of preeclamptic women and neonates (venous cord blood).


METHODS
Thirty-one preeclamptic and 30 normotensive pregnancies were recruited. The blood was fractionated using a discontinuous gradient to separate the different cell types. The messenger ribonucleic acid (mRNA) expression of GPx-1 and -4, HO-1, and Hsp-70 were analyzed by quantitative reverse transcriptase-polymerase chain reaction. GPx-1 and -4 protein level in blood cells was also detected by Western blot. The experiments were analyzed using the Student t test.


RESULTS
The HO-1 and Hsp-70 mRNA expression in whole blood was significantly higher in both fetal and maternal circulations (P < .05). We also discovered that GPx-4 mRNA was 1.6-fold higher in blood of women with preeclampsia than in control pregnancies (P = .04). The latter was associated with an increase of both GPx-1 and GPx-4 protein and mRNA levels in the lymphocyte/monocyte fraction of the blood. Significantly higher GPx-4 mRNA levels in the fetal circulation of the preeclamptic group than the control group were also detected (P < .001).


CONCLUSIONS
These data indicate that preeclampsia is associated with a specific antioxidant response in both maternal and fetal circulations, likely in response to the deleterious oxidative stress observed in this syndrome.
Boutet
Marianne
M
Unité de Recherche en Ontogénie et Reproduction, Centre de Recherche du Centre Hospitalier de l'Université Laval, and Centre de Recherche en Biologie de Reproduction, Queébec, QC, Canada.
Roland
Linda
L
Thomas
Nancy
N
Bilodeau
Jean-François
JF
D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D001792:Blood Platelets / Q000201:enzymology; D036861:Delivery, Obstetric; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000201:enzymology; D018384:Oxidative Stress / Q000502:physiology*; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D055815:Young Adult; D000094765:Glutathione Peroxidase GPX1
D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human