Role f oCaveolin-1 And Heat Shock Protein 70 (Hsp70) interation in the regulation of Nox4 expression in microdissected proximal tubules from Spontaneously Hypertensive Rats (SHR),as an effect of Losartan”.

BOCANEGRA VICTORIA; MANUCHA WALTER; GIL LORENZO ANDREA; RINALDI TOSI MARTIN; GARRAMUÑO DE VALLES PATRICIA

New York

Congreso; 15th Congress of the International Pediatric Nephrology Association (IPNA 2010) and the American Society of Pediatric Nephrology in conjunction with the 11th International Workshop on Developmental Nephrology; 2010

Objetives: we ecxamined the involvement of NHE1 associated with RhoA in the regulation of the epithelial cell apoptotic response after AT1 receptor inhibition in obstruction. NHE1 modulation of the ERK 1/2 Kinase signalo pathway was also evaluated. Methods: neonatal rats subjected to complet UUO eithin the first 48 hours of life and sham received saline, Losartan, or PD123319 AT2 inhibitor for 14 days. For apoptosis study TUNEL assay confirmes by electron mycroscopy, Bax/bcl2 espression and caspase 3 expression an activiy were performed.Western blotting and immunofluoresce were conducted for proteins expression. Results: Tubular cell apoptotic response associated with mitochondrial signaling pathway through the increased proapoptotic ratio Bax/bcl2 and consequently increased caspase 3 expression and activiy was demonstrated in Losartan obstructed kidney. Stimulation of RhoA activity that in turn reduced NHE1 expression was demonstrated in 14 day Losartan UUO kidney. Interaction between NHE1 and pERK was determinated by coimmunoprecipitation showing that membrane downregulation of NHE1 was associated with pERK overexpresssion. Absence of increased AT2 protein expression after Losartan on day 14 of obstruction was shown. PD 123319 had no protective effect on the renal response to complete 14 day UUO.Conclusions: Our findings sugest a rol of RhoA on the negative regulation of NHE1 in using phosophorylation of ERK1/2 as eventes involved in tubular cell apoptosis regulation after AT1 receptor inhibition in neonatal UUO.