EPR imaging of reducing activity in Nrf2 transcriptional factor-deficient mice.
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.
Hirayama
Aki
A
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan. aki-hira@md.tsukuba.ac.jp
Yoh
Keigyou
K
Nagase
Sohji
S
Ueda
Atsushi
A
Itoh
Ken
K
Morito
Naoki
N
Hirayama
Kouichi
K
Takahashi
Satoru
S
Yamamoto
Masayuki
M
Koyama
Akio
A
D000818:Animals; D003497:Cyclic N-Oxides / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D003952:Diagnostic Imaging; D015536:Down-Regulation; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005609:Free Radicals; D006207:Half-Life; D007668:Kidney / Q000378:metabolism*; D016350:Leucine Zippers; D008099:Liver / Q000378:metabolism*; D008181:Lupus Nephritis / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout / Q000235:genetics; D051267:NF-E2-Related Factor 2; D009929:Organ Size; D011759:Pyrrolidines / Q000008:administration & dosage; D013113:Spin Labels; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics
D003497:Cyclic N-Oxides; D004268:DNA-Binding Proteins; D005609:Free Radicals; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D011759:Pyrrolidines; D013113:Spin Labels; D015534:Trans-Activators; C077426:3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl