Levels of PPARgamma activator 15deoxy-delta 12,14prostaglandin J2 (15dPGJ2) and its effect on nitric oxide production in placenta from healthy and diabetic patients

GONZÁLEZ ELIDA; CAPOBIANCO EVANGELINA; WHITE VERÓNICA; BAIER MARIO; SALSZBERG SUSANA; PESARESI MARIO; JAWERBAUM ALICIA

Embu das Artes, Sao Paulo, Brasil.

Congreso; I Latin AmericanSymposium on Maternal Fetal Interaction. Placenta: Research and Clinical; 2003

Brazilian Society for Cell Biology-SBBC, Placenta Associations of the Americas-PAA

15deoxydelta12,14 Prostaglandin J2 (15dPGJ2) is the highest affinity endogenous ligand for PPARgamma, a nuclear receptor highly expressed in placental tissue. 15dPGJ2 has potent antiinflamatory properties and inhibits NOS activity in different cell types. Diabetes Mellitus alters the tissular expression and activity of NOS.  Aming to understand the importance of 15dPGJ2 as a modulator of nitric oxide levels in control and diabetic placenta, we evaluate the levels of 15dPGJ2, the nitric oxide production and the capability of 15dPGJ2 to modulate nitric oxide concentrations in term placental tissues from control, pregestational and gestational diabetic women. Term placental tissues from controls (n=12), Type 1 pregestational diabetic women (PGD=9) and gestational diabetic  women (GD=11) were obtained by cesarean section. 15dPGJ2 levels were measured by a commercial EIA kit. Placental explants were cultured during 3h. in the presence of 15dPGJ2 2.10-6M. After incubation nitrates were reduced to nitrites by nitrate reductase and the nitrite levels, index of NO production, were measured by the Griess reaction. 15dPGJ2 was detected in placental tissues from controls (18± 2 pg/mg), and was found reduced in GD placenta (11 ± 1 pg/mg, p<0.05), and more importantly in PGD placenta (7 ± 1 pg/mg p<0.002). Nitrate/nitrite levels  (nmol/mg) were increased in placental tisues from GD (6 ± 0.5 p<0.05) and PGD (9 ± 0.9 p<0.001) when related to controls (4 ± 0.3). In healthy palcental tisues, 15dPGJ2 additions highly reduced nitrate/nitrite levels (1 ± 0.3, p<0.001). Differently, no effect of 15dPGJ2 on NO production has been detected in GD palcenta (7 ± 1). Nitrate/nitrite levels PGD placenta were reduced by 15dPGJ2 (4 ± 0.7 p<0.01), and the addition of BADGE, a PPARgamma antagonist , enhanced nitrate/nitrite levels over their initial value (14 ± 1 p<0.01). 15dPGJ2 levels are reduced in placental tissues from GD and PGD women, probably altering the functions mediated by its receptor PPARgamma. 15dPGJ2 modulates NO production in placental tissue from healthy patients, but an alteration of this modulatory pathway is detected in placenta from GD patients. In PGD palcenta, 15dPGJ2 decreases nitrate/nitrite concentrations, a mechanism that seems to be mediated by PPARgamma. The important reduction of 15dPGJ2 levels in this tissue may be involved in the increased nitric oxide levels in placenta from PGD patients.