EPR imaging of reducing activity in Nrf2 transcriptional factor-deficient mice

Free Radic Biol Med. 2003 May 15;34(10):1236-42. doi: 10.1016/s0891-5849(03)00073-x.

Abstract

Mice that lack the Nrf2 (NF-E2-related factor 2) transcription factor develop a lupus-like autoimmune nephritis. The tissue-reducing activity of Nrf2-deficient mice was evaluated using a combination of real-time EPR imaging and spin probe kinetic analysis. Substantial delay in the spin probe 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (Carbamoyl-PROXYL) disappearance in the liver and kidneys of Nrf2-deficient mice was observed by EPR imaging. The half-life of the spin probe in the upper abdominal area was prolonged in both the Nrf2-deficient mice and in aged mice. The combination of Nrf2 deficiency and aging in female mice resulted in the most prolonged half-life of disappearance, which was four times longer than that of juvenile female mice with a wild-type genotype. These results indicate that the low reducing activity in these organs is brought about by both Nrf2 deficiency and the aging process, and it may play a key role in the onset of autoimmune nephritis. This combination of the EPR imaging and half-life analysis appears to be a very powerful tool in the real-time analysis of reducing activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic N-Oxides / administration & dosage
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / genetics
  • Diagnostic Imaging
  • Down-Regulation
  • Electron Spin Resonance Spectroscopy
  • Female
  • Free Radicals
  • Half-Life
  • Kidney / metabolism*
  • Leucine Zippers
  • Liver / metabolism*
  • Lupus Nephritis / etiology
  • Lupus Nephritis / genetics
  • Lupus Nephritis / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Mice, Knockout / genetics
  • NF-E2-Related Factor 2
  • Organ Size
  • Pyrrolidines / administration & dosage
  • Spin Labels
  • Trans-Activators / deficiency*
  • Trans-Activators / genetics

Substances

  • Cyclic N-Oxides
  • DNA-Binding Proteins
  • Free Radicals
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Pyrrolidines
  • Spin Labels
  • Trans-Activators
  • 3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl