ANGIOTENSIN AT1 RECEPTOR INHIBITION-INDUCED APOPTOSIS BY Rho-A ACTIVATION ASSOCIATED WITH Na+/K+ EXCHANGER 1 NHE1 DOWNREGULATION IN NEONATAL UNILATERAL URETERAL OBSTRUCTION (UUO).

P.G. VALLÉS; V BOCANEGRA; W. MANUCHA; A. GIL LORENZO; M. RINALDI

NEW YORK

Congreso; 15th Congress of the International Pediatric Nephrology Association (IPNA 2010) and the American Society; 2010

American Society of Pediatric Nephrology

Objetives: We examided the AT1 receptor antagonist Losartan effect on Caveolin-1 and Hsp70 protein association in SHR proximal tubules (PT). Hsp involvement on Losartan oxidative stress regulation through the MAPK signaling pathway was also studied. Methods: Five-week old SHR and controls Wistar-Kyoto rats (WKY) were randomized for receiving Losartan (40 mg/Kg/d) (SHRLos) or no treatment (SHRH2O) during 6 weeks. Interaction between proteins was determined by coimmunoprecipitation and by inmunocytochemical colocalization (confocal microscopy). Results: The relative abundance of Cav-1 eas 2 fold higher in microdissected PT membrane fractions from treated SHR vs WKYLos. Hsp70 membrane translocation was demonstrated in SHRLos through out the upregulation of Hsp70 expression in PT membrane fractions when compared with WKYH2O. Interaction between CAV-1 and Hsp70 was determined in SHRLos PT membranes. After membrane translocation of Hsp70 the decreased NADPH oxidase activity near controls demonstrated on SHRLos PT membranes was reversed by the preincubation with anti-Hsp70 antibody. Interaction between Hsp70 and NADPH oxidase subunit Nox 4 showed that PT membrane Hsp70 was associated with decreased NOx4, involving ERK1/2 activation in SRHLos. Conclusions: Interaction of Cav-1 Hsp70 was demonstrated in SHRLos tubules. Translocation of Hsp70 to PT membranes in SHRLos might exert a cytoprotective effect by downregulation of Nox 4 through the pERK1/2 pathway.