Modulation of ferritin H-chain expression in Friend erythroleukemia cells: transcriptional and translational regulation by hemin.
The mechanisms that regulate the expression of the H chain of the iron storage protein ferritin in Friend erythroleukemia cells (FLCs) after exposure to hemin (ferric protoporphyrin IX), protoporphyrin IX, and ferric ammonium citrate (FAC) have been investigated. Administration of hemin increases the steady-state level of ferritin mRNA about 10-fold and that of ferritin protein expression 20-fold. Experiments with the transcriptional inhibitor actinomycin D and transfection studies demonstrate that the increment in cytoplasmic mRNA content results from enhanced transcription of the ferritin H-chain gene and cannot be attributed to stabilization of preexisting mRNAs. In addition to transcriptional effects, translational regulation induces the recruitment of stored mRNAs into functional polyribosomes after hemin and FAC administration, resulting in a further increase in ferritin synthesis. Administration of protoporphyrin IX to FLCs produces divergent transcriptional and translational effects. It increases transcription but appears to suppress ferritin mRNA translation. FAC treatment increases the mRNA content slightly (about twofold), and the ferritin levels rise about fivefold over the control values. We conclude that in FLCs, hemin induces ferritin H-chain biosynthesis by multiple mechanisms: a transcriptional mechanism exerted also by protoporphyrin IX and a translational one, not displayed by protoporphyrin IX but shared with FAC.
Coccia
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EM
Laboratorio di Virologia, Istituto Superiore di Sanità, Rome, Italy.
Profita
V
V
Fiorucci
G
G
Romeo
G
G
Affabris
E
E
Testa
U
U
Hentze
M W
MW
Battistini
A
A
D000818:Animals; D001483:Base Sequence; D003676:Deferoxamine / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D005293:Ferritins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006427:Hemin / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D011524:Protoporphyrins / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D005290:Ferric Compounds; D011524:Protoporphyrins; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger; D006427:Hemin; D005293:Ferritins; C028025:protoporphyrin IX; D003676:Deferoxamine; C013531:ferric ammonium citrate