title: Induction of H-ferritin synthesis by oxalomalate is regulated at both the transcriptional and post-transcriptional levels.
abstract: Ferritin gene expression is complex and is controlled at transcriptional level in response to a variety of stimuli such as hormones, cytokines and cAMP. Iron, hemin and several compounds, chemically different, also activate the transcription of the ferritin gene. Ferritin biosynthesis is mainly regulated at post-transcriptional level by iron regulatory proteins (IRP1 and IRP2). We previously reported that oxalomalate, a competitive inhibitor of aconitase, remarkably decreases the IRP1 RNA-binding activity and induces a significant increase of ferritin expression. Here, we examined in cells cultured in presence of OMA the IRP1 intracellular content, ferritin biosynthesis and the transcriptional efficiency of H-ferritin gene promoter. Our results demonstrate a peculiar role of OMA that rapidly inactivates IRP1 without affecting IRP1 protein content and subsequently activates H-ferritin gene transcription leading to an overall increase of ferritin biosynthesis. We conclude that OMA regulates H-ferritin biosynthesis acting early at the post-transcriptional level and later on at transcriptional level.
authors.affiliation: Dipartimento di Farmacologia Sperimentale, Facoltà di Farmacia, Università di Napoli Federico II, via D. Montesano 49, I-80131 Napoli, Italy. rsantama@unina.it
authors.forename: Rita
authors.initials: R
authors.lastname: Santamaria
authors.forename: Maria Assunta
authors.initials: MA
authors.lastname: Bevilacqua
authors.forename: Carmen
authors.initials: C
authors.lastname: Maffettone
authors.forename: Carlo
authors.initials: C
authors.lastname: Irace
authors.forename: Barbara
authors.initials: B
authors.lastname: Iovine
authors.forename: Alfredo
authors.initials: A
authors.lastname: Colonna
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005293:Ferritins / Q000096:biosynthesis* / Q000235:genetics*; D035941:Iron Regulatory Protein 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D010070:Oxalates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D010070:Oxalates; D012333:RNA, Messenger; C015407:oxalomalic acid; D004247:DNA; D005293:Ferritins; D035941:Iron Regulatory Protein 1