INVESTIGADORES
MARTINEZ Nora Alicia
congresos y reuniones científicas
Título:
INCREASED NITRIC OXIDE PRODUCTION AND GENDER DEPENDENT CHANGES IN PPARalpha EXPRESSION AND SIGNALLING IN THE FETAL LUNG FROM DIABETIC RATS.
Autor/es:
KURTZ MELISA; MARTÍNEZ NORA; CAPOBIANCO EVANGELINA; WHITE VERÓNICA; JAWERBAUM ALICIA
Lugar:
Cambridge
Reunión:
Congreso; The 43rd Annual Meeting of DPSG; 2011
Resumen:
Maternal diabetes is associated with a wide range of adverse effects in fetal organs, including the lung. Nitric oxide (NO) is involved in lung morphogenesis and the pro-inflammatory environment is related to its overproduction. PPARá signalling has anti-inflammatory properties in several tissues, including the lung.
The aim of this work was to evaluate putative alterations in the expression and activity of PPARá, the production of NO and the expression of the inducible form of NO synthase (iNOS) in the lung from female and male fetuses from diabetic rats.
Methods: Diabetes was induced by neonatal streptozotocin administration (90 mg/kg). Fetuses from control and diabetic females were explanted on day 21 of gestation. To activate PPARá, its endogenous ligand LTB4 (0.1 µM) was injected in fetuses on days 19, 20 and 21 of pregnancy, and the fetal lung explanted on day 21 of pregnancy.
Results: We found that fetuses, placentas, and fetal lungs from diabetic rats have increased weight (p<0.05). Nitric oxide production was similar in fetal lungs from male and female fetuses, and was increased in both male and female fetal lungs from diabetic rats (p<0.05). PPARá expression was similar in fetal lungs from male and female fetuses, and was reduced only in male fetuses from diabetic rats (p <0.001). When PPARá was activated in the fetuses by its endogenous ligand, we found that the weight of the fetal lungs were reduced in the diabetic group (p< 0.05), the expression of PPARá was enhanced only in the lung from female fetuses from diabetic rats and iNOS expression was reduced both in male and female fetuses from diabetic rats.
Conclusion: Maternal diabetes leads to gender-specific defects in PPARá expression and signaling, although its activation can reduce the expression of iNOS in both female and male fetuses. Nitric oxide is overexpressed in the fetal lung form diabetic rats, an alteration that possibly affects fetal lung development and growth and that could be prevented by PPARá activation.