Selenium regulation of transcript abundance and translational efficiency of glutathione peroxidase-1 and −4 in rat liver

2001 ◽  
Vol 357 (3) ◽  
pp. 851-858 ◽  
Author(s):  
Sherri WEISS SACHDEV ◽  
Roger A. SUNDE
Keyword(s):  
Glutathione Peroxidase ◽  
Rat Liver ◽  
Transcript Abundance ◽  
Translational Efficiency ◽  
Mrna Levels ◽  
Glutathione Peroxidase 1 ◽  
Relative Contribution ◽  
Se Deficiency ◽  
Selenoprotein Mrnas ◽  
Se Status

Glutathione peroxidase (GPX)1 mRNA in rat liver falls dramatically during Se deficiency to levels that are approx. 10% of Se-adequate levels. This regulation is mediated by mRNA stability, and is hypothesized to involve nonsense-mediated mRNA decay. mRNA levels for GPX4 and other selenoproteins are much less regulated by Se status. To evaluate the relative contribution of mRNA abundance versus translational efficiency to overall regulation of GPX1 expression, we quantified GPX1, GPX4 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcripts per cell in rat liver. Surprisingly, we found that GPX1 transcripts in Se deficiency are moderately abundant and similar in abundance to GAPDH and other selenoprotein mRNAs; Se supplementation increases GPX1 mRNA so that it is 30-fold higher than GAPDH mRNA. Translational efficiency of GPX1 mRNA is half of that of GPX4. Translational efficiency of GPX1 mRNA increases approx. 20-fold with Se supplementation and appears to switch GPX1 mRNA from nonsense-mediated degradation to translation. This regulatory switch can explain why GPX1 expression is an excellent parameter for assessment of Se status.

scholarly journals Selenium Requirements Are Higher for Glutathione Peroxidase-1 mRNA than Gpx1 Activity in Rat Testis

2009 ◽  
Vol 234 (5) ◽  
pp. 513-521 ◽  
Author(s):  
Sonja C. Schriever ◽  
Kimberly M. Barnes ◽  
Jacqueline K. Evenson ◽  
Anna M. Raines ◽  
Roger A. Sunde
Keyword(s):  
Glutathione Peroxidase ◽  
Critical Role ◽  
Cell Types ◽  
Pcr Analysis ◽  
Testis Weight ◽  
Mrna Levels ◽  
Response Curves ◽  
Lower Priority ◽  
Selenoprotein Mrnas ◽  
Se Status

Selenium (Se) plays a critical role in testis, sperm, and reproduction, and testis Se levels are remarkably maintained in Se deficiency. In most other tissues, Se levels decrease dramatically as do levels of most selenoproteins and levels of a subset of Se-regulated selenoprotein mRNAs. Because of the recent identification of key molecules in the targeted trafficking of Se to the testis, we examined the hierarchy of Se regulation in testis by determining the dietary Se regulation of the full testis selenoproteome in rats fed graded levels of Se (0 to 0.8 μg Se/g) as Na2SeO3 for 28 d. Se status did not significantly affect testis weight or glutathione peroxidase 4 (Gpx4) activity ( P > 0.05). qRT-PCR analysis of selenoprotein mRNA expression revealed that 21 of the 24 selenoprotein mRNAs and ApoER2 mRNA (the selenoprotein P [Sepp1] receptor) were also not regulated significantly by dietary Se status. In contrast, Gpx1 activity decreased to 28% of Se-adequate levels, and mRNA levels for Gpx1, Sepp1, and Sepw1 (selenoprotein W) decreased significantly in Se-deficient rats to 45, 46, and 55%, respectively, of Se-adequate plateau levels. Overlap of hyperbolic Gpx4 activity and Sepw1 mRNA response curves with testis Se concentration, all with minimum dietary Se requirements <0.016 μg Se/g, showed the priority for synthesis of Gpx4. Higher minimum dietary Se requirements of 0.04 μg Se/g for Gpx1 activity and Sepp1 mRNA, and the even higher minimum dietary Se requirement of 0.08 μg Se/g for Gpx1 mRNA, suggest that the hierarchy of these biomarkers reflects distinct, lower priority pools, cell types, and roles for Se within the testis.

scholarly journals Longitudinal selenium status in healthy British adults: assessment using biochemical and molecular biomarkers

2008 ◽  
Vol 99 (S3) ◽  
pp. S37-S47 ◽  
Author(s):  
Roger A. Sunde ◽  
Elaine Paterson ◽  
Jacqueline K. Evenson ◽  
Kimberly M. Barnes ◽  
Julie A. Lovegrove ◽  
...  
Keyword(s):  
Molecular Biology ◽  
Glutathione Peroxidase ◽  
Biochemical Markers ◽  
Molecular Biomarkers ◽  
Mrna Levels ◽  
Phospholipid Hydroperoxide Glutathione Peroxidase ◽  
Response Curves ◽  
Glutathione Peroxidase 1 ◽  
Longitudinal Effects ◽  
Se Status

Human selenium (Se) requirements are currently based on biochemical markers of Se status. In rats, tissue glutathione peroxidase-1 (Gpx1) mRNA levels can be used effectively to determine Se requirements; blood Gpx1 mRNA levels decrease in Se-deficient rats, so molecular biology-based markers have potential for human nutrition assessment. To study the efficacy of molecular biology markers for assessing Se status in humans, we conducted a longitudinal study on 39 subjects (age 45 ± 11) in Reading, UK. Diet diaries (5 day) and blood were obtained from each subject at 2, 8, 17 and 23 weeks, and plasma Se, glutathione peroxidase (Gpx3) enzyme activity, and selenoprotein mRNA levels were determined. There were no significant longitudinal effects on Se biomarkers. Se intake averaged 48 ± 14 μg/d. Plasma Se concentrations averaged 1·13 ± 0·16 μmol/l. Plasma Se v. energy-corrected Se intake (ng Se/kJ/d) was significantly correlated, but neither Gpx3 activity v. Se intake (ng Se/kJ/d) nor Gpx3 activity v. plasma Se was significantly correlated. Collectively, this indicates that subjects were on the plateaus of the response curves. Selenoprotein mRNAs were quantitated in total RNA isolated from whole blood, but mRNA levels for Gpx1, selenoprotein H, and selenoprotein W (all highly regulated by Se in rodents), as well selenoprotein P, Gpx3, and phospholipid hydroperoxide glutathione peroxidase were also not significantly correlated with plasma Se. Thus selenoprotein molecular biomarkers, as well as traditional biochemical markers, are unable to further distinguish differences in Se status in these Se replete subjects. The efficacy of molecular biomarkers to detect Se deficiency needs to be tested in Se-deficient populations.

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

2009 ◽  
Vol 29 (5) ◽  
pp. 329-338 ◽  
Author(s):  
Roger A. Sunde ◽  
Anna M. Raines ◽  
Kimberly M. Barnes ◽  
Jacqueline K. Evenson
Keyword(s):  
Thioredoxin Reductase ◽  
Selenium Deficiency ◽  
Underlying Mechanism ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Nonsense Mediated Decay ◽  
Liver And Kidney ◽  
Se Deficiency ◽  
Selenoprotein Mrnas ◽  
Se Status

Gpx (glutathione peroxidase)-1 enzyme activity and mRNA levels decrease dramatically in Se (selenium) 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 on Se-deficient, Se-marginal and Se-adequate diets (0, 0.05 and 0.2 μg of 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 Sedeficient liver and kidney respectively. Importantly, nine selenoprotein mRNAs in liver and fifteen selenoprotein mRNAs in the 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.

scholarly journals Effects of Dietary Selenium Deficiency or Excess on Selenoprotein Gene Expression in the Spleen Tissue of Pigs

Animals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1122 ◽  
Author(s):  
Zhuang Lu ◽  
Pengzu Wang ◽  
Teng Teng ◽  
Baoming Shi ◽  
Anshan Shan ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Thioredoxin Reductase ◽  
Selenium Deficiency ◽  
Type I ◽  
Mrna Levels ◽  
Spleen Tissue ◽  
Selenoprotein K ◽  
Selenoprotein Genes ◽  
Se Deficiency ◽  
Selenoprotein M

To evaluate the effects of dietary Se deficiency and excess on the mRNA levels of selenoproteins in pig spleen tissues, 20 healthy uncastrated boars (Duroc × Landrace × Yorkshire, 10 ± 0.72 kg) were randomly divided into four groups (5 pigs per group). The pigs were fed a Se deficient corn-soybean basal feed (Se content <0.03 mg/kg) or basal feed with added sodium selenite at 0.3, 1.0, or 3.0 mg Se/kg diet, respectively. The experiment lasted 16 weeks. The spleen tissue was collected to examine the mRNA expression levels of 24 selenoprotein genes at the end of the study. Compared with pigs in other groups, those fed with the 1.0 mg Se/kg diet had higher mRNA levels of glutathione peroxidase 1 (Gpx1), glutathione peroxidase 2 (Gpx2), deiodinase type II (Dio2), thioredoxin reductase 3 (Txnrd3), selenoprotein H (Selh), selenoprotein N, 1 (Sepn1), selenoprotein P1 (Sepp1), and selenoprotein V (Selv) in the spleen (p < 0.05). Dietary Se deficiency resulted in lower mRNA levels of Gpx1, Gpx2, glutathione peroxidase 3 (Gpx3), Dio2, thioredoxin reductase 2 (Txnrd2), Txnrd3, Selh, selenoprotein I (Seli), selenoprotein K (Selk), selenoprotein M (Selm), Sepn1, Sepp1, and Selv in the spleen than the other three groups. Dietary Se levels did not affect the mRNA levels of glutathione peroxidase 4 (Gpx4), deiodinase type I (Dio1), deiodinase type III (Dio3), selenophosphate synthetase 2 (Sephs2), thioredoxin reductase 1 (Txnrd1), selenoprotein O (Selo), selenoprotein S (Sels), selenoprotein W (Selw), selenoprotein X (Selx), and selenoprotein 15 (Sel15) in the spleen (p > 0.05). Dietary Se levels can affect the transcription levels of 14 selenoprotein genes in the spleen of pigs.

Blood Glutathione Peroxidase-1 mRNA Levels Can Be Used as Molecular Biomarkers to Determine Dietary Selenium Requirements in Rats

2009 ◽  
Vol 234 (11) ◽  
pp. 1271-1279 ◽  
Author(s):  
Roger A. Sunde ◽  
Kevin M. Thompson ◽  
Jacqueline K. Evenson ◽  
Britta M. Thompson
Keyword(s):  
Glutathione Peroxidase ◽  
Molecular Biomarkers ◽  
Mrna Levels ◽  
Dietary Selenium ◽  
Glutathione Peroxidase 1

scholarly journals Assessment of Glutathione Peroxidase-1 (GPX1) Gene Expression as a Specific Diagnostic and Prognostic Biomarker in Malignant Pleural Mesothelioma

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2285
Author(s):  
Amal F. Gharib ◽  
Muhammad Alaa Eldeen ◽  
Amany Salah Khalifa ◽  
Wael H. Elsawy ◽  
Emad Mohamed Eed ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glutathione Peroxidase ◽  
Malignant Pleural Mesothelioma ◽  
Success Factors ◽  
Malignant Tumors ◽  
University Hospital ◽  
Pleural Mesothelioma ◽  
Mrna Levels ◽  
Expression Levels ◽  
Glutathione Peroxidase 1

Malignant pleural mesothelioma (MPM) is a malignant tumor of the mesothelial lining of the thorax. It has been related to frequent exposure to asbestos. Diagnosis of malignant pleural mesothelioma is considered a criticizing problem for clinicians. Early diagnosis and sufficient surgical excision of MPM are considered the cornerstone success factors for the management of early MPM. Glutathione peroxidase-1 (GPX1) is an intracellular protein found to be extensively distributed in all cells, and it belongs to the GPX group. In the current study, we included ninety-eight patients with MPM that underwent surgery at the Zagazig University Hospital in Egypt. We assessed GPX1 gene expression level as it was thought to be related to pathogenicity of cancer in a variety of malignant tumors. We observed a significant elevation in GPX1-mRNA levels in MPM relative to the nearby normal pleural tissues. It was found to be of important diagnostic specificity in the differentiation of MPM from normal tissues. Moreover, we studied the survival of patients in correlation to the GPX1 expression levels and we reported that median overall survival was about 16 months in patients with high GPX1 expression levels, while it was found to be about 40 months in low GPX1 levels.

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