The senescence-accelerated mouse prone-8 (SAM-P8) oxidative stress is associated with upregulation of renal NADPH oxidas

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ORIGINAL PAPER

The senescence-accelerated mouse prone-8 (SAM-P8) oxidative stress is associated with upregulation of renal NADPH oxidase system Ana Baltanás & Maria E. Solesio & Guillermo Zalba & María F. Galindo & Ana Fortuño & Joaquín Jordán

Received: 14 March 2013 / Accepted: 28 June 2013 # University of Navarra 2013

Abstract Herein, we investigate whether the NADPH oxidase might be playing a key role in the degree of oxidative stress in the senescence-accelerated mouse prone-8 (SAM-P8). To this end, the activity and expression of the NADPH oxidase, the ratio of glutathione and glutathione disulfides (GSH/GSSG), and the levels of malonyl dialdehyde (MDA) and nitrotyrosine (NT) were determined in renal tissue from SAM-P8 mice at the age of 1 and 6 months. The senescence-accelerated-resistant mouse (SAM-R1) was used as control. At the age of 1 month, NADPH oxidase activity and Nox2 protein expression were higher in SAM-P8 than in SAM-R1 mice. However, we found no differences in the GSH/GSSG ratio, MDA, NT, and Nox4 levels between both groups of animals. At the age of 6 months, SAM-R1 mice in comparison to A. Baltanás : G. Zalba : A. Fortuño (*) Division of Cardiovascular Sciences, Center for Applied Medical Research, University of Navarra, Pío XII 55, 31008 Pamplona, Spain e-mail: [email protected] M. E. Solesio : M. F. Galindo Translational Neuropsychopharmacology Unit, Albacete University Hospital Center, Albacete, Spain G. Zalba Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain

SAM-P8 mice showed an increase in NADPH oxidase activity, which is associated with higher levels of NT and increased Nox4 and Nox2 expression levels. Furthermore, we found oxidative stress hallmarks including depletion in GSH/GSSG ratio and increase in MDA levels in the kidney of SAM-P8 mice. Finally, NADPH oxidase activity positively correlated with Nox2 expression in all the animals (r=0.382, P