Post-transcriptional regulation of glutathione peroxidase gene expression by selenium in the HL-60 human myeloid cell line

Abstract

We have used a cloned cDNA for the major human selenoprotein, glutathione peroxidase (GPx), to assess the mode of regulation of human GPx gene (GPX-1) expression by selenium. When the HL-60 human myeloid cell line is grown in a selenium-deficient medium, GPx enzymatic activity decreases 30-fold compared with selenium-replete cells. Upon return to a medium containing selenium in the form of selenite, GPx activity in the cells starts to increase within 48 hours and reaches maximal (selenium-replete) levels at 7 days. Steady-state immunoreactive protein levels correlate with enzymatic activity. Cycloheximide inhibits the rise in GPx activity that accompanies selenium replenishment, indicating that protein synthesis is required for the increase. However, GPx mRNA levels and the rate of transcription of the human GPx gene change very little and thus appear to be independent of the selenium supply. Thus the human GPx gene appears to be regulated post-transcriptionally, probably cotranslationally, in response to selenium availability.

Loss of heterozygosity of the human cytosolic glutathione peroxidase I gene in lung cancer

“…Several in vitro and in vivo studies have shown that selenium exposure increases GPxl activity and RNA expression, although not GPXI gene transcription (15,(33)(34)(35)(36)(37). Numerous case-control epidemiological studies have examined the relationship of serum selenium levels and the risk of lung cancer (38)(39)(40)(41)(42).…”

“…The GPXI 5' flanking sequence in seven lung tumor specimens was amplified by primers which spanned the 802 bp sequence between RHOA and GPXI. After treatment with a DNA purification system (Promega) the nucleotide sequence of the PCR fragments was determined using primers end-labeled with [ / y- 33 P]ATP and T4 DNA polynucleotide kinase (Promega). The sequencing reactions were performed in a Perkin Elmer 9600 thermal cycler using a thermal cycle sequencing kit (Stratagene) according to the manufacturer's instructions and size-fractionated on a 6% polyacrylamide gel.…”

Differential regulation of glutathione peroxidase by selenomethionine and hyperoxia in endothelial cells

“…The relationship between selenium supply and GP enzyme activity has received extensive investigation, and it is now clear that GP activity in tissues and cells depends on the availability of selenium. Selenium deficiency results in a decrease in GP protein detectable by immunoprecipitation [2][3][4][5], and in enzyme activity [2,[4][5][6][7]. On the other hand, tissue GP activity and protein can be increased in individuals with low selenium intake by dietary supplementation with certain selenium-containing compounds [2,4,6].…”

“…On the other hand, tissue GP activity and protein can be increased in individuals with low selenium intake by dietary supplementation with certain selenium-containing compounds [2,4,6]. Similarly, selenium-deficient cells transferred to seleniumreplete medium showed an increase in GP activity and immunoreactive protein [2,5]. However, the underlying molecular mechanisms of the regulation of GP activity by selenium remain largely controversial.…”

Subcellular Localization of Glutathione Peroxidase, Change in Glutathione System during Ageing and Effects on Cardiometabolic Risks and Associated Diseases

“…The latter is encoded by UGA and directed by the selenocysteine insertion sequence, SECIS element [28,29], which serves as a platform for the recruitment of elongation factors of selenocysteine-tRNA [Ser]Sec (Sec-tRNA [Ser] Sec ) translation that decodes the UGA codon for the whole family of selenoproteins. The exogenous Se supply controls the enzymatic activity of human GPx1 without affecting the level of GPx1 mRNA, suggesting that the human GPx1 gene is posttranscriptionally regulated by Se [30].…”