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

J Neurosci Res. 2015 Nov;93(11):1728-39. doi: 10.1002/jnr.23627. Epub 2015 Aug 6.


Superoxide dismutases (SODs) are the primary reactive oxygen species (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. Because of the SOD2 strategic location, it represents the first mechanism of defense against the augmentation of ROS/reactive nitrogen species levels in the mitochondria for preventing further damage. This study seeks 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, because of the known interaction between SOD2 and p53 protein, this study seeks to clarify the impact that the double mutation has on oxidative/nitrative stress levels in the brain of mice carrying the double mutation (p53(-/-) × SOD2(-/+) and p53(-/-) × TgSOD2). We show that each mutation affects mitochondrial, nuclear, and cytosolic oxidative/nitrative stress basal levels differently, but, overall, no change or reduction of oxidative/nitrative stress levels was found in the whole-brain homogenate. The analysis of well-known antioxidant systems such as thioredoxin-1 and Nrf2/HO-1/BVR-A suggests their potential role in the maintenance of the cellular redox homeostasis in the presence of changes of SOD2 and/or p53 protein levels.

Keywords: MnSOD; p53; RRID:AB_10618757; RRID:AB_10850321; RRID:AB_1840351; RRID:AB_2049199; RRID:AB_2256876; RRID:AB_476744; RRID:AB_881705; RRID:AB_958795; biliverdin reductase-A; heme oxygenase-1; oxidative stress.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Western
  • Brain / metabolism*
  • Mice
  • Mice, Mutant Strains
  • Mitochondria / metabolism
  • Nitrosation
  • Oxidative Stress / physiology*
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*


  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • Superoxide Dismutase
  • superoxide dismutase 2