TY - JOUR T1 - Iron Chelator-Mediated Alterations in Gene Expression: Identification of Novel Iron-Regulated Molecules that are Molecular Targets of HIF-1α and p53 JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.109.061028 SP - mol.109.061028 AU - Federica Saletta AU - Yohan Suryo Rahmanto AU - Egarit Noulsri AU - Des R Richardson Y1 - 2009/12/18 UR - http://molpharm.aspetjournals.org/content/early/2009/12/18/mol.109.061028.abstract N2 - Iron-deficiency affects 500 million people, yet the molecular role of iron in gene expression remains poorly characterized. In addition, the alterations in global gene expression after iron chelation remain unclear and are important to assess for understanding the molecular pathology of iron-deficiency and the biological effects of chelators. Considering this, we assessed the effect on whole genome gene expression of two iron chelators (desferrioxamine and 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone) that have markedly different permeability properties. Sixteen genes were significantly regulated by both ligands, while a further fifty genes were significantly regulated by either compound. Apart from iron-mediated regulation of expression via hypoxia inducible factor-1α, it was of interest that the transcription factor p53 was also involved in iron-regulated gene expression. Examining sixteen genes regulated by both chelators in normal and neoplastic cells, five genes (APP, GDF15, CITED2, EGR1 and PNRC1) were significantly differentially expressed between the cell types. In view of their functions in tumor suppression, proliferation and apoptosis, these findings are important for understanding the selective anti-proliferative effects of chelators against neoplastic cells. Most of the genes identified have not been previously described to be iron-regulated and are important for understanding the molecular and cellular effects of iron-depletion.The American Society for Pharmacology and Experimental Therapeutics ER -