Cytoprotective effects of Hsp70 and antioxidant transcription factor Nrf2 in Neonatal obstructive nephropaty

RINALDI TOSI MARTÍN; BOCANEGRA VICTORIA; MANUCHA WALTER; BENARDON MARIA EUGENIA; GARRAMUÑO VALLES PATRICIA

Congreso; XXVIII Reunión Anual de la Sociedad de Biologia de Cuyo; 2010

An important mechanism by which cells adapt to oxidant stress is to transcriptionally up-regulate a distinct array of cytoprotective genes responsible for buffering the cells’ antioxidant capacity. In this study, we examined Nrf2 transcription factor and Hsp70 expression on oxidative stress modulation in neonatal unilateral ureteral obstruction (UUO). Rats were subjected to UUO (n=5) within the first 48h of life. After 7, 10 and 14 days of obstruction, nephrectomy was performed. The expression of Hsp70, Nrf2 and Keap1 were studied by WB; NADPH-oxidase and total antioxidant status (TAS) activity were performed. After 14 days of obstruction, decreased Hsp70 protein expression associated with Nrf2 protein cytosolic downregulation, linked to increased Keap1   expression, were shown. Oxidative stress induction was shown by NADPH oxidase activity and decreased TAS 14 days after obstruction. Conversely, 7 and 10 days after kidney obstruction, increased Hsp70 expression and cytosolic Keap1 linked to  nuclear Nrf2 expression that leads to enhanced antioxidant glutathione S-transferase (GSTA2) gene with absence of oxidative response was demonstrated. These findings suggest that induction of Hsp70 and Nrf2 expression are involved on obstruction- oxidative stress resistance.