Post-transcriptional regulation of glutathione peroxidase gene expression by selenium in the HL-60 human myeloid cell line
Chada, Sunil ; Whitney, Constance ; Newburger, Peter E.
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Cell Differentiation
Cell Nucleus
Cycloheximide
Gene Expression Regulation, Leukemic
Glutathione Peroxidase
Humans
Leukemia, Myeloid
Protein Biosynthesis
RNA, Messenger
Selenium
Transcription, Genetic
Tumor Cells, Cultured
Cancer Biology
Cell and Developmental Biology
Hematology
Medical Genetics
Pediatrics
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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.
Source
Blood. 1989 Nov 15;74(7):2535-41.