Basal brain oxidative and nitrative stress levels are finely regulated by the interplay between superoxide dismutase 2 and p53

Superoxide dismutases (SODs) are the primary ROS scavenging enzymes of the cell and catalyze the dismutation of superoxide radicals O2−. to H2O2 and molecular oxygen (O2). Among the three forms of SOD identified manganese-containing SOD (MnSOD, SOD2) is a homotetramer located wholly in the mitochondrial matrix. Due to SOD2 strategic location, it represents the first mechanism of defense against the augmentation of reactive oxygen/reactive nitrogen species (ROS/RNS) levels in the mitochondria in order to prevent further damages. Here, we aimed to understand the effects that the partial lack (SOD2(−/+)) or the overexpression (TgSOD2) of MnSOD produces on oxidative/nitrative stress basal levels in different brain-isolated cellular fractions (i.e. mitochondrial, nuclear, cytosolic) as well as in the whole brain homogenate. Furthermore, due to the known interaction between SOD2 and p53 protein, we aimed to clarify the impact that the double mutation has on oxidative/nitrative stress levels in the brain of the new mice carrying the double mutation (p53(−/−)xSOD2(−/+)) and (p53(−/−)xTgSOD2). Interestingly, we found that each mutation differently affects (i) mitochondrial; (ii) nuclear; and (iii) cytosolic oxidative/nitrative stress basal levels; but, overall, no changes or a reduction of oxidative/nitrative stress levels were found in the whole brain homogenate. Finally, the analysis of well-known antioxidant systems such as thioredoxin-1 and the Nrf2/HO-1/BVR-A system suggested their potential role in the maintenance of the cellular redox homeostasis in the presence of changes of SOD2 and/or p53 protein levels.