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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #190405


item Uthus, Eric

Submitted to: Biological Trace Element Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/6/2006
Publication Date: 3/1/2007
Citation: Uthus, E.O., Moskovitz, J. 2007. Specific activity of methionine sulfoxide reductase in CD-1 mice is significantly affected by dietary selenium but not zinc. Biological Trace Element Research. 115:265-275.

Interpretive Summary: Protein oxidation occurs when certain oxygen containing compounds (which occur naturally in the body) cause damage to specific amino acids in protein. Amino acids are the building blocks of proteins. This damage can be detrimental if the amino acids are not repaired. One enzyme that repairs damaged methionine (a sulfur containing amino acid in proteins) is methionine sulfoxide reductase. Recently it was shown that there are 2 forms of this enzyme, one of which contains selenium and zinc. This enzyme, called MsrB, does not function without selenium but it is not known how important the zinc is for function. Thus, a study was done to determine the effects of dietary selenium and zinc on MsrB activity. Mice were fed diets containing 0 or 0.2 µg selenium/g and 3 or 15 µg zinc/g. The dietary requirement of selenium for the mouse is about 0.2 µg/g diet; the requirement for zinc is about 12 µg/g diet. Thus, the mice fed no selenium were selenium deficient and those fed 3 µg zinc/g diet were marginally deficient in zinc. After 9.5 wk MsrB enzyme activity was measured in brain, kidney, and liver. Selenium deficiency decreased the activity of MsrB in all 3 tissues but marginal zinc had no direct effect. In liver, the ratio of damaged methionine in protein (caused by protein oxidation) to normal methionine in the same protein was increased by selenium deficiency. This indicates that selenium deficiency results in oxidative damage. The results of this study show that selenium deficiency causes an increased oxidation of methionine in protein, that dietary selenium status affects MsrB activity, and that marginal zinc deficiency has little effect on MsrB activity. Therefore, dietary selenium is probably more important than dietary zinc in maintaining beneficial action of the enzyme MsrB.

Technical Abstract: Reactive oxygen species (ROS)-mediated oxidation of methionine residues in protein results in a racemic mixture of R and S forms of methionine sulfoxide (MetO). MetO is reduced back to methionine by the methionine sulfoxide reductases MsrA and MsrB. MsrA is specific toward the S form and MsrB is specific toward the R form of MetO. MsrB is a selenoprotein reported to contain zinc. To determine the effects of dietary selenium (Se) and zinc (Zn) on Msr activity, CD-1 mice (N=16/group) were fed, in a 2x2 design, diets containing 0 or 0.2 ug Se (as selenite)/g and 3 or 15 ug Zn/g. As an oxidative stress, half of the mice received L-buthionine sulfoximine (BSO; i.p.; 2 mmol/kg, 3 times/wk for the last 3 wk); the others received saline. After 9.5 wk Msr (the combined specific activities of MsrA and MsrB) was measured in brain, kidney, and liver. Se deficiency decreased (p<0.0001 Msr in all 3 tissues but Zn had no direct effect. BSO treatment was expected to result in increased Msr activity; this was not seen. Surprisingly, BSO treatment slightly, but significantly, decreased (p<0.002) kidney Msr. A three-way interaction (Se x Zn x BSO/Saline) affected brain Msr. Compared to Msr activity in Se-deficient mice, Msr activity was increased by Se supplementation in each respective Zn-BSO/Saline group except in the mice fed 15 ug Zn/g and injected with saline. In this group, supplementation with Se did not result in an increase in Msr activity. Additionally, we found that the ratio of MetO to methionine in liver protein was increased (indicative of oxidative damage) by Se deficiency. The reuslts show Se deficiency increases oxidation of methionyl residues in protein, that Se status affects Msr (most likely through effects on the selenoprotein MsrB), that marginal Zn deficiency has little effect on Msr in liver and kidney. However, a three-way interaction among Se, Zn and BSO/Sal affected brain Msr activity. Finally, the results show that the oxidative effects of limited BSO treatment did not up-regulate Msr activity.