Effects of intracellular chelatable iron and oxidative stress on transcription of classical cellular glutathione peroxidase gene in murine erythroleukemia cells.
The effect of intracellular chelatable iron levels and of oxidative stress on nuclear classical cellular glutathione peroxidase (GSHPx-1) RNA nascent chain elongation (run-on transcription) and on the stability of cytoplasmic GSHPx-1 mRNA was investigated in murine erythroleukemia (MEL) cells. The amount of iron in the intracellular low molecular mass iron pool was changed by incubation of MEL cells transformed by Friend virus with iron donors or iron chelators. Transcription in vitro in isolated nuclei from treated cells showed that the treatment with iron chelators (desferrioxamine (DFO), pyridoxal isonictinoyl hydrazone (PIH) decreased the rate of nuclear GSHPx-1 RNA nascent chain elongation in both uninduced and with 5 mmol hexamethylenebisacetamide (HMBA) to erythroid differentiation induced MEL cells. Iron donors (diferric transferrin, Fe-PIH or their combination) and t-butyl hydroperoxide (t-BuOOH) had the opposite effect on GSHPx-1 gene transcription in run-on experiments. On the other hand, 50 mumol DFO or 2.5 mumol t-BuOOH did not change the stability of cytoplasmic GSHPx-1 mRNA in both uninduced and induced MEL cells treated with 5 mumol actinomycin D and with or without these agents for 9 h. These findings indicate that iron and oxidative stress play their role at the transcriptional level of GSHPx-1 gene expression.
Fuchs
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Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D015672:Erythroid Precursor Cells / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology / Q000235:genetics; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010545:Peroxides / Q000494:pharmacology; D014158:Transcription, Genetic; D014168:Transferrin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D020122:tert-Butylhydroperoxide
D000081:Acetamides; D007502:Iron Chelating Agents; D010545:Peroxides; D014168:Transferrin; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D007501:Iron; D005979:Glutathione Peroxidase; C014026:hexamethylene bisacetamide