15-Deoxy-Δ12,14-prostaglandin J2 and peroxisome proliferator-activated receptor γ (PPARγ) levels in term placental tissues from control and diabetic rats: modulatory effects of a PPARγ agonist on nitridergic and lipid placental metabolism
E. Capobianco A , A. Jawerbaum A C , M. C. Romanini B , V. White A , C. Pustovrh A , R. Higa A , N. Martinez A , M. T. Mugnaini B , C. Soñez B and E. Gonzalez A
+ Author Affiliations
- Author Affiliations
A Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Serrano 669, (1414) Buenos Aires, Argentina.
B Departamento de Anatomía Animal, Facultad de Agronomía y Veterinaria, Universidad Nacional de Río Cuarto, (5800) Córdoba, Argentina.
C Corresponding author. Email: a.jawerbaum@abaconet.com.ar
Reproduction, Fertility and Development 17(4) 423-433 https://doi.org/10.1071/RD04067
Submitted: 30 June 2004 Accepted: 18 December 2004 Published: 15 March 2005
Abstract
15-Deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) is a peroxisome proliferator-activated receptor γ (PPARγ) ligand that regulates lipid homeostasis and has anti-inflammatory properties in many cell types. We postulated that 15dPGJ2 may regulate lipid homeostasis and nitric oxide (NO) levels in term placental tissues and that alterations in these pathways may be involved in diabetes-induced placental derangements. In the present study, we observed that, in term placental tissues from streptozotocin-induced diabetic rats, 15dPGJ2 concentrations were decreased (83%) and immunostaining for nitrotyrosine, indicating peroxynitrite-induced damage, was increased. In the presence of 15dPGJ2, concentrations of nitrates/nitrites (an index of NO production) were diminished (40%) in both control and diabetic rats, an effect that seems to be both dependent on and independent of PPARγ activation. Exogenous 15dPGJ2 did not modify lipid mass, but decreased the incorporation of 14C-acetate into triacylglycerol (35%), cholesteryl ester (55%) and phospholipid (32%) in placenta from control rats, an effect that appears to be dependent on PPARγ activation. In contrast, the addition of 15dPGJ2 did not alter de novo lipid synthesis in diabetic rat placenta, which showed decreased levels of PPARγ. We conclude that 15dPGJ2 modulates placental lipid metabolism and NO production. The concentration and function of 15dPGJ2 and concentrations of PPARγ were altered in placentas from diabetic rats, anomalies probably involved in diabetes-induced placental dysfunction.
Acknowledgments
This work was supported by grants PIP 0598/98 (E. G.) and PIP 2529/99 (A. J.) from Consejo Nacional de Investigaciones Científicas y Técnicas and by Agencia de Promoción Científica y Tecnológica de Argentina (PICT 05-10652; E. G.). The authors thank María Ester Castro for her expert technical assistance.
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