Selenium deficiency activates mouse liver Nrf2-ARE but vitamin E deficiency does not.
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.
Burk
Raymond F
RF
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0252, USA. raymond.burk@vanderbilt.edu
Hill
Kristina E
KE
Nakayama
Akihiro
A
Mostert
Volker
V
Levander
Ximena A
XA
Motley
Amy K
AK
Johnson
Delinda A
DA
Johnson
Jeffrey A
JA
Freeman
Michael L
ML
Austin
Lori M
LM
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017353:Gene Deletion; D005982:Glutathione Transferase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D011808:Quinone Reductases / Q000378:metabolism; D012643:Selenium / Q000172:deficiency*; D014811:Vitamin E Deficiency / Q000378:metabolism*
D000975:Antioxidants; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D011808:Quinone Reductases; D005982:Glutathione Transferase; D012643:Selenium