Publication: Iron chelator-mediated alterations in gene expression: Identification of novel iron-regulated molecules that are molecular targets of hypoxia-inducible factor-1α and p53
Issued Date
2010-03-01
Resource Type
ISSN
15210111
0026895X
0026895X
Other identifier(s)
2-s2.0-77149125234
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular Pharmacology. Vol.77, No.3 (2010), 443-458
Suggested Citation
Federica Saletta, Yohan Suryo Rahmanto, Egarit Noulsri, Des R. Richardson Iron chelator-mediated alterations in gene expression: Identification of novel iron-regulated molecules that are molecular targets of hypoxia-inducible factor-1α and p53. Molecular Pharmacology. Vol.77, No.3 (2010), 443-458. doi:10.1124/mol.109.061028 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/28777
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Iron chelator-mediated alterations in gene expression: Identification of novel iron-regulated molecules that are molecular targets of hypoxia-inducible factor-1α and p53
Other Contributor(s)
Abstract
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, whereas a further 50 genes were significantly regulated by either compound. Apart from ironmediated regulation of expression via hypoxia inducible factor-1α, it was noteworthy that the transcription factor p53 was also involved in iron-regulated gene expression. Examining 16 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 antiproliferative effects of chelators against neoplastic cells. Most of the genes identified have not been described previously to be iron-regulated and are important for understanding the molecular and cellular effects of iron depletion. Copyright © 2010 The American Society for Pharmacology and Experimental Therapeutics.