Ferrochelatase, glutathione peroxidase and transferrin receptor mRNA synthesis and levels in mouse erythroleukemia cells.

Abstract

Mouse erythroleukemia Friend cells induced to undergo erythroid differentiation by treatment with hexamethylenebisacetamide (HMBA) were shown to increase cytoplasmic ferrochelatase mRNA, transferrin receptor (TfR) mRNA and glutathione peroxidase (GSHPx) mRNA levels. Inhibition of heme synthesis at the level of 5-aminolevulinic acid synthase by isonicotinic acid hydrazide (INH) and D,L-penicillamine (PA) or at the level of 5-aminolevulinic acid dehydratase by succinylacetone (SA) decreased the expression of ferrochelatase mRNA and TfR mRNA. In contrast with these mRNAs, the synthesis and the levels of glutathione peroxidase mRNA increased by the addition of these inhibitors of heme synthesis. The amount of iron in the intracellular low molecular mass iron pool detected in the post-mitochondrial supernatant of Friend cells treated with heme synthesis inhibitors was increased. On the other hand, iron levels in this pool declined with the preincubation of Friend cells with iron chelator pyridoxal isonicotinoylhydrazone (PIH). Further treatment with PIH or desferrioxamine (Desferal) increased the synthesis of TfR mRNA in induced Friend cells. The synthesis of ferrochelatase mRNA declined by the same treatment. The opposite was observed when the iron level in the low molecular mass intracellular nonheme iron pool was elevated by treatment with either diferric transferrin (Fe-Tf) or ferric pyridoxal isonicotinoylhydrazone (Fe-PIH). Exogenously supplied hemin stimulated the synthesis of ferrochelatase mRNA in uninduced Friend cells, while the synthesis of this mRNA in Friend cells taken on the fifth day after induction was inhibited by the addition of hemin.