Specific activity of methionine sulfoxide reductase in CD-1 mice is significantly affected by dietary selenium but not zinc.
Reactive oxygen species-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 (Zn). To determine the effects of dietary selenium (Se) and Zn on Msr activity, CD-1 mice (N=16/group) were fed, in a 2 x 2 design, diets containing 0 or 0.2 microg Se/g and 3 or 15 microg Zn/g. As an oxidative stress, half of the mice received L-buthionine sulfoximine (BSO; ip; 2 mmol/kg, three times per week 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 the brain, kidney, and liver. Se deficiency decreased (p<0.0001) Msr in all three tissues, but Zn had no direct effect. BSO treatment was expected to result in increased Msr activity; this was not seen. Additionally, we found that the ratio of MetO to methionine in liver protein was increased (indicative of oxidative damage) by Se deficiency. The results show that Se deficiency increases oxidation of methionyl residues in protein, that Se status affects Msr (most likely through effects on the selenoprotein MsrB), and that marginal Zn deficiency has little effect on Msr in liver and kidney. Finally, the results show that the oxidative effects of limited BSO treatment did not upregulate Msr activity.
Uthus
Eric O
EO
US Department of Agriculture, ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202, USA.
Moskovitz
Jackob
J
D000818:Animals; D003545:Cysteine / Q000097:blood; D004032:Diet; D005978:Glutathione / Q000097:blood; D006710:Homocysteine / Q000097:blood; D008297:Male; D051150:Methionine Sulfoxide Reductases; D051379:Mice; D008954:Models, Biological; D010088:Oxidoreductases / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species; D012643:Selenium / Q000032:analysis / Q000097:blood / Q000494:pharmacology*; D014131:Trace Elements / Q000032:analysis; D015854:Up-Regulation; D015032:Zinc / Q000032:analysis / Q000378:metabolism*
D017382:Reactive Oxygen Species; D014131:Trace Elements; D006710:Homocysteine; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D005978:Glutathione; D012643:Selenium; D015032:Zinc; D003545:Cysteine; D010100:Oxygen