NEONATAL UNILATERAL URETERAL OBSTRUCTION (UUO): NITRIC OXIDE IN MITOCHONDRIAL APOPTOSIS PATHWAY

MAC LNTOSH N, RUETE C, CARRIZO L. MANUCHA W, GARRAMUÑO VALLÉS P

Mendoza.Argentina

Congreso; XXIII Annual Scientific Meeting. Cuyo Biology Society; 2005

Cuyo Biology Society

NEONATAL UNILATERAL URETERAL OBSTRUCTION (UUO): NITRIC OXIDE IN MITOCHONDRIAL APOPTOSIS PATHWAY Mac lntosh N, Ruete C, Carrizo L. Manucha W, Garramuño  Vallés P. Fac Cs Méd. Univ Nac Cuyo-CONICET. 5500 Mendoza.   Neonatal obstructive nephropathy, a main cause of chronic renal failure in infancy, is characterized by epithelial cell apoptosis lead­ing to tubular atrophy. We have studied nitric oxide (NO) involve­ment in the mitochondrial apoptosis pathway in unilateral ureteral obstruction (UUO). In vivo experiments were performed in control and neonatal rats with UOO for 14 days .ln vitro experiments were done in control and obstructed cortex homogenates (CC and OC), in the presence of L-NAME 20 mmol/L or sodium nitroprusside (SNP) 200 µmo1/L for 24 h. Apoptosis induction, demonstrated in UUO by an increased number of apoptotic cells in cortical collect­ing ducts, increased expression of Bax/BcL2, ratio, and caspase 3 activity was shown to be associated with decreased mRNA iNOS expression and lower nitrite generation. CC in the presence of L-­NAME decreased nitrites release with an increase in caspase 3 ac­tivity and proapoptotic Bax/Bcl2 ratio expression. On the con­trary, in the presence of the NO- donor, SNP, increased nitrite generation with a simultaneous decrease in the expression of the proapoptotic Bax/BcL2 ratio and caspase 3 activity near baseline levels were demonstrated, in control and obstructed cortex homogenates. From our results, a cytoprotective role of nitric ox­ide for mitochondrial apoptosis induction in neonatal ureteral ob­struction may be suggested.