Selenium deficiency activates mouse liver Nrf2-ARE but vitamin E deficiency does not

Raymond F. Burk, Kristina E. Hill, Akihiro Nakayama, Volker Mostert, Ximena A. Levander, Amy K. Motley, Delinda A. Johnson, Jeffrey A. Johnson, Michael L. Freeman, Lori M. Austin

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


Selenium (Se) and vitamin E are antioxidant micronutrients. Se functions through selenoproteins and vitamin E reacts with oxidizing molecules in membranes. The relationship of these micronutrients with the Nrf2-antioxidant response element (ARE) pathway was investigated using ARE-reporter mice and Nrf2-/- mice. Weanling males were fed Se-deficient (0 Se), vitamin E-deficient (0 E), or control diet for 16 or 22 weeks. The ARE reporter was elevated 450-fold in 0 Se liver but was not elevated in 0 E liver. Antioxidant enzymes induced by Nrf2-ARE (glutathione S-transferase (GST), NAD(P)H quinone oxidoreductase (NQOR), and heme oxygenase-1 (HO-1)) were elevated in 0 Se livers but not in 0 E livers. Deletion of Nrf2 had varying effects on the inductions, with GST induction being abolished by it but induction of NQOR and HO-1 still occurring. Thus, Se deficiency, but not vitamin E deficiency, induces a number of enzymes that protect against oxidative stress and modify xenobiotic metabolism through Nrf2-ARE and other stress-response pathways. We conclude that Se deficiency causes cytosolic oxidative stress but that vitamin E deficiency does not. This suggests that the oxidant defense mechanisms in which these antioxidant nutrients function are independent of one another.

Original languageEnglish (US)
Pages (from-to)1617-1623
Number of pages7
JournalFree Radical Biology and Medicine
Issue number8
StatePublished - Apr 15 2008
Externally publishedYes


  • Cytosolic oxidant defense network
  • Free radicals
  • Mouse liver
  • Nrf2 ARE pathway
  • Oxidative stress
  • Phase II enzymes
  • Selenium deficiency
  • Vitamin E deficiency

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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