Selenium status highly regulates selenoprotein mRNA levels for only a subset of the selenoproteins in the selenoproteome

Abstract

Synopsis Gpx (glutathione peroxidase)-1 enzyme activity and mRNA levels decrease dramatically in selenium (Se) deficiency, whereas other selenoproteins are less affected by Se deficiency. This hierarchy of Se regulation is not understood, but the position of the UGA selenocysteine codon is thought to play a major role in making selenoprotein mRNAs susceptible to nonsense-mediated decay. Thus in the present paper we studied the complete selenoproteome in the mouse to uncover additional selenoprotein mRNAs that are highly-regulated by Se status. Mice were fed Se-deficient, Se-marginal, and Se-adequate diets (0, 0.05 and 0.2 μg Se/g, respectively) for 35 days, and selenoprotein mRNA levels in liver and kidney were determined using microarray analysis and quantitative real-time PCR analysis. Se-deficient mice had liver Se concentrations and liver Gpx1 and thioredoxin reductase activities that were 4, 3 and 3%, respectively, of the levels in Se-adequate mice, indicating that the mice were Se-deficient. mRNAs for Selh (selenoprotein H) and Sepw1 (selenoprotein W) as well as Gpx1 were decreased by Se deficiency to <40% of Se-adequate levels. Five and two additional mRNAs were moderately down-regulated in Se-deficient liver and kidney, respectively. Importantly, nine selenoprotein mRNAs in liver and fifteen selenoprotein mRNAs in kidney were not significantly regulated by Se deficiency, clearly demonstrating that Se regulation of selenoprotein mRNAs is not a general phenomenon. The similarity of the response to Se deficiency suggests that there is one underlying mechanism responsible. Importantly, the position of the UGA codon did not predict susceptibility to Se regulation, clearly indicating that additional features are involved in causing selenoprotein mRNAs to be sensitive to Se status.

Insights for Setting of Nutrient Requirements, Gleaned by Comparison of Selenium Status Biomarkers in Turkeys and Chickens versus Rats, Mice, and Lambs

“…These studies were conducted concurrently with a rat study, and the determinations of selenium concentrations in the liver and diet; of GPX1, GPX4, and GPX3 activities; and of GPX1, GPX4, and SEPP1 transcript levels were all conducted as previously described in detail (15). Additional data are from a study that used the same mouse strain supplemented with 0, 0.05, and 0.2 mg Se/g as Na 2 SeO 3 (22). Selenium biomarker data for turkey poults are from the report of Taylor and Sunde (26), which used a basal selenium-deficient 30% torula-yeast diet supplemented with 7% crystallized amino acids and with graded levels of dietary selenium from 0 to 1.0 mg Se/g as Na 2 SeO 3 .…”

“…These additional selenoproteins expanded the array of both biochemical and transcript-based biomarkers of selenium status in our studies (14)(15)(16)(17)(18). The identification of the complete selenoproteome (19) further expanded the number of selenoprotein transcripts as "molecular biomarkers" for the assessment of selenium status and requirements in rodents (20)(21)(22)(23) and is helping researchers to better understand the hierarchy of selenium incorporation into selenoproteins.…”

The differential expression of glutathione peroxidase 1 and 4 depends on the nature of the SECIS element

“…In selenium deficient mice, Gpx1, SelH and SelW mRNA levels markedly decrease to < 40% of selenium adequate levels. 48,49 Some other selenoprotein mRNAs, including TR1, TR2, SelP, SelK, SelM and Gpx3 were only moderately affected by low selenium conditions, while the majority of selenoprotein mRNA levels remained unaffected by selenium deficiency or supplementation. 49 Another possible layer of regulation, that is not yet completely elucidated, is the mechanism of UGA decoding by the dedicated tRNA Sec .…”

Selenium Inhibits Renal Oxidation and Inflammation But Not Acute Kidney Injury in an Animal Model of Rhabdomyolysis

“…Its affinity for H 2 O 2 is greater than catalase, making it an efficient antioxidant (60). It is also the most Se-sensitive selenoprotein, making it a good marker for intrinsic selenium status (51). Our study aims to investigate the impact of Se supplementation on markers for AKI following experimental RM.…”