[Show abstract][Hide abstract] ABSTRACT: 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.
Full-text · Article · May 2008 · Free Radical Biology and Medicine
[Show abstract][Hide abstract] ABSTRACT: The brain and testis retain selenium better than other tissues during selenium deficiency. Studies of mice with selenoprotein P (Sepp1) deleted (Sepp1(-/-) mice) showed that brain and testis selenium levels are largely dependent on Sepp1. Therefore, we examined tissue selenium in mice fed varying amounts of selenium and in Sepp1(-/-) mice to characterize better the role(s) of Sepp1. Mice were fed a selenium-deficient diet for 8 wk supplemented with selenium as selenite from none to 0.25 mg/kg diet and tissue selenium was measured. Brain and testis maintained their selenium better than did liver, kidney, and muscle when dietary selenium was limiting but testis selenium fell sharply in the group fed the deficient diet. Brain retained its selenium well, even in the group fed the deficient diet. After intravenous injection of (75)Se-Sepp1 into Sepp1(-/-) and Sepp1(+/+) mice, qualitative differences between brain and testis (75)Se uptake were noted, further suggesting differences in their uptake of selenium from Sepp1. Finally, selenium was measured in brain regions of Sepp1(-/-) and Sepp1(+/+) mice fed the diet supplemented with 1 mg selenium/kg and Sepp1(+/+) mice fed the deficient diet. Deletion of Sepp1 and selenium deficiency each lowered selenium a similar amount in cortex, midbrain, brainstem, and cerebellum. Selenium in the hippocampus was lowered by deletion of Sepp1 but not by selenium deficiency. These results suggest that Sepp1 is more important for maintaining selenium in the hippocampus than in other brain regions. They also confirm the position of the brain at the apex of the organ selenium hierarchy.
Preview · Article · Apr 2007 · Journal of Nutrition
[Show abstract][Hide abstract] ABSTRACT: Heme oxygenase (HO)-1 is induced by oxidative stress and protects against oxidant injury. We examined the effect of rapid induction of hepatic HO-1 on serum iron level. Serum iron was approximately doubled within 6 h when HO-1 was induced by phenobarbital treatment of selenium-deficient mice. Blocking heme synthesis with diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) prevented the induction of HO-1 and the rise in serum iron. DDC did not block HO-1 induction by hemin. Inhibition of HO activity by tin protoporphyrin prevented a rise in serum iron that occurred following phorone treatment. These results indicate that heme synthesis or an exogenous source of heme is needed to allow induction of HO-1. Further, they link HO-1 induction with a rise in serum iron, suggesting that the iron resulting from catabolism of heme by HO-1 is released by the liver.
No preview · Article · Feb 2007 · Drug Metabolism Reviews