Cytoprotective Role of Nrf2 Pathway and Hsp70 in Neonatal Unilateral Obstruction

RINALDI TOSI MARTÍN; BOCANEGRA VICTORIA; MANUCHA WALTER; GIL LORENZO ANDREA; GARRAMUÑO VALLÉS , PATRICIA

Congreso; The First South American Spring Symposium in Signal Transduction and Molecular Medicine (SISTAM 2010); 2010

We analyzed the Hsp70 response and the Nrf2 transcription factor signal transduction on UUO oxidative stress modulation. Rats were subjected to UUO or sham operation and kidneys harvested at 5, 7, 10 and 14 days after obstruction.Hsp70 and Nrf2 activity and its downstream target gene products were assessed. After 10 and 14 days of obstruction, enhanced lipid peroxidation through higher TBARS levels and reduced total antioxidant activity and enhanced NADPH oxidase activity were demonstrated. This was accompanied by decreased inducible Hsp70 expression and a progressive reduction of nuclear Nrf2 and its gene products GSTA2 and NQO1, whereas the Nrf2 repressor Keap1 was upregulated. By contrast, on early obstruction for 7 days;lack of increased oxidative markers associated with higher inducible Hsp70 protein levels and a rapid nuclear accumulation of Nrf2, Keap1 downregulation and mRNA induction of the identified Nrf2-dependent genes, NQO1 and GSTA2, were shown.We suggest that the cytoprotection in early obstruction depends on the combined contribution of induced activation of Nrf2 upregulating its downstream gene products and Hsp70 response.Impaired ability to mount the biological response to the prevailing oxidative stress leading to renal injury was shown in prolonged obstruction.