CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
MMP-1 and MMP-9 activities are modulated by nitric oxide in fetal heart and placenta of diabetic rats at mid-gestation
Autor/es:
PUSTOVRH, CAROLINA; JAWERBAUM, ALICIA; CAPOBIANCO, EVANGELINA; WHITE, VERÓNICA; NORA MARTÍNEZ; HIGA, R.; LÓPEZ COSTA, J.J.; PAZ, D.; ELIDA TERESA GONZALEZ
Lugar:
Cambridge, Gran Bretaña
Reunión:
Congreso; 33rd Annual Meeting of the Fetal and Neonatal Physiological Society; 2006
Institución organizadora:
Fetal and Neonatal Physiological Society
Resumen:
Diabetic pathology produces placental and fetal alterations that involved the increases of matrix metalloproteinases (MMPs). MMPs are important enzymes associated with tissue remodelling, growth and differentiation. These enzymes could be modulated by different agents who disrupt its cysteine switch leading to its activation. In other tissues, nitric oxide (NO) is able to promote MMPs activation. The aim of the present work was to evaluate the localization of MMPs and nitric oxide synthase (NOS) and to study the influence of NO on MMP-2 and MMP-9 activities in the feto-placental unit from control and diabetic rats. Methodology: Rats were made diabetics by neonatal administration of streptozotocin (90mg/kg)  a method that leads to mild hyperglycemia (150-230 mg/dl) in the adult. Fetal and placental tissues (maternal and fetal placental sides) from diabetic rats (D) and controls (C) were evaluated on day 13.5 of pregnancy. MMPs and iNOS distribution were evaluated by double inmunolabeling using confocal microscopy. NO synthase (NOS) activity was evaluated in situ by NADPH-diaphorase (NADPH-d) histochemistry. The effect of NO on MMP2 and MMP9 activities was measured after 1 h. incubation with or without additions of of either a NO donor (sodium nitroprusside (NP) 600 mM) or a NOS inhibitor (L-NAME 600 mM). Results: NADPH-d activity was enhanced in D placenta when compared to C, mostly in the labyrinth zone. In C and D placenta, NP additions increased MMP9 activity (30%, p<0.05) in the maternal side while NAME additions reduced MMP9 and MMP2 activities in both maternal (22%, p<0.05) and fetal (20%, p<0.05) sides.  In C and D heart fetuses, NADPH-d activity was enhanced in D when compared to C. MMP2 and iNOS label presented different expressions in D and C fetus and showed colocalization in the  ventricular septum. In the fetuses, NP additions increased MMP2 activity (30% and 48% respectively, p<0.01) while NAME reduced its activity (25% and 40% respectively, p<0.01). Conclusions: Our results showed that MMPs activities are up-regulated by NO. In maternal diabetes, overactivation of MMPs in the feto-placental unit may be the result of increased NO levels and probably lead to abnormal remodeling processes.