Disease relevance of Sep15

• Selenium deficiency is known to be associated with male infertility, and the selenoprotein PHGPx has been shown to increase in rat testis after puberty and to depend on gonadotropin stimulation in hypophysectomized rats [Roveri et al. (1992) J. Biol. Chem. 267, 6142 6146] [1].
• These data may offer alternative explanations for the established toxicity of tellurium via disruption of selenoprotein function, particularly by the induction of intracellular oxidative stress by the inhibition of Se-dependent glutathione peroxidase [2].
• These results suggest that ID-I is a selenoprotein and that Se deficiency can exacerbate the hypothyroidism observed in iodine deficiency [3].
• We report the isolation and characterization of a new selenoprotein from a human lung adenocarcinoma cell line, NCI-H441 [4].
• These results show that with the strategy utilized here, the capacity of selenoprotein synthesis in E. coli is more than sufficient for making possible the use of the bacteria for production of recombinant selenoproteins [5].

High impact information on Sep15

• Selenocysteine is incorporated cotranslationally at UGA codons, normally read as stop codons, in several bacterial proteins and in the mammalian proteins glutathione peroxidase (GPX), selenoprotein P and Type I iodothyronine 5' deiodinase (5'DI) [6].
• Dual function of the selenoprotein PHGPx during sperm maturation [7].
• A new selenoprotein from human lung adenocarcinoma cells: purification, properties, and thioredoxin reductase activity [4].
• Conserved nucleotide sequences in the open reading frame and 3' untranslated region of selenoprotein P mRNA [8].
• Selenoprotein P cDNA has been cloned from human liver and heart cDNA libraries and sequenced [8].

Chemical compound and disease context of Sep15

• Selenoprotein P induced in Leydig cells following cAMP stimulation may counteract O2 toxicity from cAMP-mediated increases in testosterone production [9].

Biological context of Sep15

• This report provides the first example of the ER-resident selenoprotein and suggests a possible role of the trace element selenium in the quality control of protein folding [10].
• Pathogenesis of diquat-induced liver necrosis in selenium-deficient rats: assessment of the roles of lipid peroxidation and selenoprotein P [11].
• Testosterone mediates expression of the selenoprotein PHGPx by induction of spermatogenesis and not by direct transcriptional gene activation [1].
• During selenium deficiency there is a differential regulation of selenoprotein synthesis and gene expression; for example, there is a decrease in abundance of mRNA for cytosolic glutathione peroxidase (cGSH-Px) and a preservation of mRNA for phospholipid-hydroperoxide glutathione peroxidase (PHGSH-Px) [12].
• The aim of the present work was to assess the role of cGSH-Px and PHGSH-Px 3' untranslated regions (UTRs) in the regulation of selenoprotein mRNA stability and translation by using H4-II-E-C3 cells transfected with different constructs containing a type I iodothyronine deiodinase-coding region linked to different selenoprotein mRNA 3' UTRs [12].

Anatomical context of Sep15

• Nonsense-mediated decay of mRNA for the selenoprotein phospholipid hydroperoxide glutathione peroxidase is detectable in cultured cells but masked or inhibited in rat tissues [13].
• RPA detected significant mRNA expression for at least 1 selenoprotein in all tissues except pancreas [14].
• Effect of selenium on selenoprotein P expression in cultured liver cells [15].
• The striking burst of PHGPx expression at the transition of round to elongated spermatids suggests an involvement of this selenoprotein in sperm maturation [1].
• The expression of PHGPX in testes is consistent with the previously described specific requirement for selenium for synthesis of a 15-20-kDa selenoprotein which is related to the production of functional spermatozoa [16].

Associations of Sep15 with chemical compounds

• 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 [17].
• The effect of dithiothreitol on secretion of selenoprotein P by H4IIE cells was examined [15].
• These findings raise the possibility that selenoprotein P protects cell membranes against oxidant injury and that glutathione is involved in that protection [18].
• In adult male rats, selenium deficiency results in a near complete loss in the selenoprotein 5'-deiodinase in the liver, resulting in decreased peripheral deiodination of thyroxine (T4) and increased serum T4 concentrations [19].
• After the two columns were separated, selenoprotein P was eluted with heparin from heparin-Sepharose and albumin eluted from reactive blue with high salt [20].

Physical interactions of Sep15

• SBP2 also interacts specifically with the minimally functional 3' UTR of another selenoprotein mRNA, deiodinase 1 [21].

Regulatory relationships of Sep15

• Selenoprotein P concentration was proportional to dietary selenium level up to 0.1 mg/kg and was a greater percentage of control values than was glutathione peroxidase activity [22].
• A type III iodothyronine deiodinase (D-III) that inactivates thyroid hormones has been recently cloned and identified as a selenoprotein in neonatal rat skin [23].

Other interactions of Sep15

• Growth, and mRNA levels for selenoprotein P, 5'-deiodinase, and GPX4 were not decreased by Se deficiency [24].
• Purification, redox sensitivity, and RNA binding properties of SECIS-binding protein 2, a protein involved in selenoprotein biosynthesis [21].
• Evidence that type III iodothyronine deiodinase in rat astrocyte is a selenoprotein [23].
• The concentration of selenoprotein P fell at approximately the same rate in the rats fed the selenium-deficient diet as did plasma glutathione peroxidase activity [22].
• Recently, we have characterized a Xenopus laevis cDNA (XL-15) that encodes a selenoprotein with type III deiodinase activity (St. Germain, D.L., Schwartzman, R., Croteau, W., Kanamori, A., Wang, Z., Brown, D.D., and Galton, V.A. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 7767-7771) [25].

Analytical, diagnostic and therapeutic context of Sep15

• A competitive radioimmunoassay for selenoprotein P was developed [26].
• Using mobility shift assays, we could show that a protein, present in different types of mammalian cell extracts, possesses the capacity of binding the SECIS element of the selenoprotein glutathione peroxidase (GPx) mRNA [27].
• An analytical method that uses two different high-performance liquid chromatography (HPLC) columns in tandem has been developed that separates three major selenium-containing proteins (albumin, glutathione peroxidase, and selenoprotein P) found in human blood plasma [28].
• Thus selenium chemoprevention efficacy can be separated experimentally from selenoprotein synthesis using this model system [29].
• When proteins in brain and liver homogenates and subcellular fractions where separated by one-dimensional SDS-PAGE and exposed to X-ray film, the resulting autoradiograms revealed the existence of seven distinct selenoprotein bands in brain and eight in liver [30].

References