Modulation of nitric oxide concentration and lipid metabolism by 15-deoxy Delta12,14prostaglandin J2 in embryos from control and diabetic rats during early organogenesis.
The concentration of 15-deoxy Delta(12,14)PGJ(2) (15dPGJ(2)) and its effects on nitric oxide generation and neutral lipid in embryos from control and neonatal streptozotocin-induced (n-stz) diabetic rats during organogenesis were investigated. 15dPGJ(2) is produced in embryos during organogenesis, and its production is lower in embryos of n-stz diabetic rats than in embryos from control rats. Nitrate and nitrite concentrations were higher in embryos from n-stz diabetic rats and were reduced in the presence of 15dPGJ(2) both in embryos from control and diabetic rats. Thus, decreased 15dPGJ(2) concentrations in embryos from n-stz diabetic rats may be related to the high nitric oxide concentrations found in those embryos. Exogenous 15dPGJ(2) decreased cholesterol and cholesteryl ester concentrations in embryos from control and n-stz diabetic rats, and reduced triacylglycerol concentrations in control embryos. Incorporation of [(14)C]acetate into lipids showed decreased de novo synthesis of cholesteryl ester and triacylglycerides in embryos from n-stz diabetic rats compared with controls. Exogenous 15dPGJ(2) reduced the incorporation of [(14)C]acetate into triacylglycerides, cholesterol and cholesteryl ester in embryos from both control and n-stz diabetic rats. 15dPGJ(2) is present in embryos during organogenesis, and reduces embryonic nitric oxide production and lipid synthesis. The lower 15dPGJ(2) concentration in embryos from n-stz diabetic rats may result in developmental alterations in this diabetic model.
Jawerbaum
A
A
Centro de Estudios Farmacologicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Serrano 669, (1414) Buenos Aires, Argentina. a.jawerbaum@abaconet.com.ar
Sinner
D
D
White
V
V
Pustovrh
C
C
Capobianco
E
E
Gonzalez
E
E
D000085:Acetates / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D046508:Culture Techniques; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D008074:Lipoproteins / Q000378:metabolism; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000032:analysis; D038081:Organogenesis / Q000502:physiology; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000085:Acetates; D002788:Cholesterol Esters; D008055:Lipids; D008074:Lipoproteins; D009566:Nitrates; D009573:Nitrites; D014280:Triglycerides; C039160:lipoprotein cholesterol ester, human; D009569:Nitric Oxide; D002784:Cholesterol; D015230:Prostaglandin D2