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Impact of Glutathione Peroxidase-1 (Gpx1) Genotype on Selenoenzyme and Transcript Expression When Repleting Selenium-Deficient Mice

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Abstract

Glutathione peroxidase (Gpx1) is the major selenoprotein in most tissues in animals. Knockout (KO) of Gpx1 decreases Gpx1 activity to near zero and substantially reduces liver selenium (Se) levels, but has no overt effects in otherwise healthy mice. To investigate the impact of deletion of Gpx1 on Se metabolism, Se flux, and apparent Se requirements, KO, Gpx1 heterozygous (Het), and Gpx1 wild-type (WT) mice were fed Se-deficient diet for 17 weeks, then repleted with graded levels of Se (0–0.3 μg Se/g as Na2SeO3) for 7 days, and selenoprotein activities and transcripts were determined in blood, liver, and kidney. Se deficiency decreased the activities of plasma Gpx3, liver Gpx1, liver Txnrd, and liver Gpx4 to 3, 0.3, 11, and 50% of WT Se-adequate levels, respectively, but the Gpx1 genotype had no effect on growth or changes in activity or expression of selenoproteins other than Gpx1. Se repletion increased selenoprotein transcripts to Se-adequate levels after 7 days; Se response curves and apparent Se requirements for selenoprotein transcripts were similar to those observed in studies starting with Se-adequate mice. With short-term Se repletion, selenoenzyme activities resulted in three Se response curve patterns: (1) liver and kidney Gpx1, Gpx4, and Txnrd activities were sigmoidal or hyperbolic with breakpoints (0.08–0.19 μg Se/g) that were double those observed in studies starting with Se-adequate mice; (2) red blood cell Gpx1 activity was not significantly changed; and (3) plasma Gpx3 activity only increased substantially with 0.3 μg Se/g. Plasma Gpx3 is secreted from kidney. In this short-term study, kidney Gpx3 mRNA reached plateau levels at 0.1 μg Se/g, and other kidney selenoenzyme activities reached plateau levels at ≤ 0.2 μg Se/g, so sufficient Se should have been present in kidney. Thus, the delayed increase in plasma Gpx3 activity suggests that newly synthesized and secreted kidney Gpx3 is preferentially retained in kidney or rapidly cleared by binding to basement membranes in kidney or in other tissues. This repletion study shows that loss of capacity to incorporate Se into Gpx1 in Gpx1 KO mice does not dramatically alter expression of other Se biomarkers, nor the short-term flux of Se from intestine to liver to kidney.

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Acknowledgements

This research was supported by the University of Wisconsin Selenium Nutrition Research Fund (No. 12046295), and by an undergraduate University of Wisconsin Cargill-Benevenga Research Stipend (to JAL).

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Authors and Affiliations

  1. Department of Nutritional Sciences, University of Wisconsin, 1415 Linden Drive, Madison, WI, 53706, USA

    Roger A. Sunde, Edward T. Zemaitis II, Andrew B. Blink & Julia A. Lawinger

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  1. Roger A. Sunde
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  2. Edward T. Zemaitis II
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  3. Andrew B. Blink
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  4. Julia A. Lawinger
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Contributions

All authors participated in the review of the manuscript. JAL and RAS mixed diets and conducted the mouse study; ETZ, ABB, and RAS conducted the selenoenzyme assays; ETZ and RAS conducted the qPCR assays; RAS conducted the statistics and wrote the manuscript.

Corresponding author

Correspondence to Roger A. Sunde.

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The animal protocol was approved by the Animal Care and Use Committee at the University of Wisconsin-Madison (protocol A005368).

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Sunde, R.A., Zemaitis, E.T., Blink, A.B. et al. Impact of Glutathione Peroxidase-1 (Gpx1) Genotype on Selenoenzyme and Transcript Expression When Repleting Selenium-Deficient Mice. Biol Trace Elem Res 186, 174–184 (2018). https://doi.org/10.1007/s12011-018-1281-6

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