15-Deoxy-Delta12,14-prostaglandin J2 and peroxisome proliferator-activated receptor gamma (PPARgamma) levels in term placental tissues from control and diabetic rats: modulatory effects of a PPARgamma agonist on nitridergic and lipid placental metabolism.
15-Deoxy-Delta(12,14)-prostaglandin J2 (15dPGJ2) is a peroxisome proliferator-activated receptor (3) (PPAR(3)) 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 PPAR(3) activation. Exogenous 15dPGJ2 did not modify lipid mass, but decreased the incorporation of (14)C-acetate into triacylglycerol (35%), cholesteryl ester (55%) and phospholipid (32%) in placenta from control rats, an effect that appears to be dependent on PPAR(3) activation. In contrast, the addition of 15dPGJ2 did not alter de novo lipid synthesis in diabetic rat placenta, which showed decreased levels of PPAR(3). We conclude that 15dPGJ2 modulates placental lipid metabolism and NO production. The concentration and function of 15dPGJ2 and concentrations of PPAR(3) were altered in placentas from diabetic rats, anomalies probably involved in diabetes-induced placental dysfunction.
Capobianco
E
E
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Cientĩcas y Técnicas (CONICET), Buenos Aires, Argentina.
Jawerbaum
A
A
Romanini
M C
MC
White
V
V
Pustovrh
C
C
Higa
R
R
Martinez
N
N
Mugnaini
M T
MT
Soñez
C
C
Gonzalez
E
E
D000085:Acetates / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D050356:Lipid Metabolism / Q000187:drug effects*; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000633:toxicity; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000085:Acetates; D001786:Blood Glucose; D009566:Nitrates; D009573:Nitrites; D047495:PPAR gamma; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D013311:Streptozocin; D015230:Prostaglandin D2