PPARgamma activation regulates nitric oxide levels in term placental tissues from control and diabetic rats

CAPOBIANCO, E; JAWERBAUM A., ROMANINI, CRISTINA; SOÑEZ, CARLOS; WHITE, VERÓNICA; PUSTOVRH, CAROLINA; GONZÁLEZ, ELIDA

Buenos Aires, Argentina

Congreso; 12th Biennial Meeting of the International Society for Free Radical Research; 2004

International Society for Free Radical Research

The peroxisome proliferator-activated receptor gamma (PPARgamma), essential for normal placental development is activated by 15-deoxy-delta 12,14 prostaglandin J2 (15dPGJ2). 15dPGJ2 negatively regulates placental NO production. In diabetes, alterations in NO production and oxidative stress are induced. Objective: Placenta from control (C) and diabetic (D) rats at term were studied to determine: 1) 15dPGJ2 levels (EIA, pg/mg) and PPARgamma expression (immunohistochemistry), 2) the involvement of PPARgamma on the regulation of NO levels (nitrates/nitrites by Griess reaction), 3) peroxynitrite induced damage by evaluation of nitrotyrosine residues and apoptosis (immunohistochemistry). The placenta was incubated in the presence or absence of 15dPGJ2 (2 microM) or BADGE (100 microM, PPARgamma antagonist). Results: 15dPGJ2 levels were lower in D (1.1± 0.4) than in C (13.8 ± 7.4 p<0.001). PPARgamma expression was reduced in diabetic rats compared to control. Badge induced an increase in nitrates/nitrites levels in both (61%, p<0.001) and D (68%, p<0.001) placenta. An increased staining for nitrotyrosine was found surrounding the vessels in D placental slides. Conclusions: The low levels of PPARgamma and 15dPGj2 observed in placentas from diabetic rats may be involved in the abnormal regulation of placental blood flow. In addition, NO leads to the formation of peroxynitirites, probably involved in the apoptosis of cells that injuries the placenta.