Differential regulation of ferritin expression in Friend leukemia cells by iron compounds.
Ferritin is an ubiquitous iron storage protein that plays a key role in determining the intracellular fate of iron. Therefore, ferritin synthesis is highly regulated by the iron status of the cell through post-transcriptional mechanisms that involve a specific high-affinity interaction between an iron-responsive element (IRE) in the 5' untranslated region of ferritin mRNA and a 98 kDa cytoplasmic protein, the iron-regulatory factor (IRF). The mechanisms that regulate the expression of the iron storage protein ferritin were investigated in erythroid (Friend erythroleukemia cell, FLC) and fibroblastic (L929 and B6) cell lines after exposure to various iron compounds. Both hemin (ferric protoporphyrin IX) and iron (as ferric ammonium citrate, FAC) were used as inducers of ferritin synthesis. Administration of hemin increases ferritin synthesis 8-12 fold both in erythroid and in non-erythroid cell lines, whereas FAC is a weak inducer of ferritin in FLC (only 5-fold). These results correlate with ferritin mRNA expression in FLC observed after hemin treatment compared to the effect exerted by FAC administration. This differential effect suggests that heme is the physiological compound able to stimulate ferritin synthesis in erythroid cell lines and that it plays an important physiological role in regulating gene expression in developing erythroid cells.
Coccia
E M
EM
Laboratory of Virology, Istituto Superiore di Sanità, Roma, Italy.
Stellacci
E
E
Perrotti
E
E
Marziali
G
G
Battistini
A
A
D003676:Deferoxamine / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology*; D005293:Ferritins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014176:Protein Biosynthesis; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011990:Receptors, Transferrin / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005290:Ferric Compounds; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D006427:Hemin; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine; C013531:ferric ammonium citrate