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Prepublished online as a Blood First Edition Paper on September 26, 2002; DOI 10.1182/blood-2002-07-2140. This Article Full Text (PDF) All Versions of this Article: 2002-07-2140v1 101/9/3690    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Muckenthaler, M. Articles by Hentze, M. W Search for Related Content PubMed PubMed Citation Articles by Muckenthaler, M. Articles by Hentze, M. W Social Bookmarking                   What's this? Submitted July 18, 2002 Accepted August 15, 2002 Relationships and distinctions in iron regulatory networks responding to interrelated signals Martina Muckenthaler, Alexandra Richter, Niki Gunkel, Dieter Riedel, Maria Polycarpou-Schwarz, Sabine Hentze, Mechthild Falkenhahn, Wolfgang Stremmel, Wilhelm Ansorge, and Matthias W Hentze* Department of Gene Expression, European Molecular Biology Laboratory, Heidelberg, Germany Intervet International, Schwabenheim, Germany Department of Medicine, University of Heidelberg, Heidelberg, Germany Department of Biocomputing, Krebsforschungszentrum, Heidelberg, Germany * Corresponding author; email: hentze{at}embl-heidelberg.de. Specialized cDNA-based microarrays were developed to investigate complex physiological gene regulatory patterns in iron metabolism. Approximately 120 human cDNAs were strategically selected to represent genes involved either in iron metabolism or in interlinked pathways (e.g. oxidative stress, NO metabolism or copper metabolism), and immobilized on glass slides. HeLa cells were treated with iron donors or iron chelators, or were subjected to oxidative stress (H2O2) or NO (sodiumnitroprusside). In addition, we generated a stable transgenic HeLa cell line expressing the HFE gene under an inducible promoter. Gene response patterns were recorded for all of these interrelated experimental stimuli, and analyzed for common and distinct responses that define signal-specific regulatory patterns. The resulting regulatory patterns reveal and define degrees of relationship between distinct signals. Remarkably, the gene responses elicited by the altered expression of the hemochromatosis protein HFE and by pharmacological iron chelation exhibit the highest degree of relatedness, both for IRP- and non-IRP target genes. This finding suggests that HFE expression directly affects the intracellular chelatable iron pool in the transgenic cell line. Furthermore, cells treated with the iron donors hemin or ferric ammonium citrate display response patterns that permit the identification of the iron loaded state in both cases, and to discriminate between the sources of iron loading. These findings also demonstrate the broad utility of gene expression profiling with the "IronChip" to study iron metabolism and related human diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. C. Sammarco, S. Ditch, A. Banerjee, and E. Grabczyk Ferritin L and H Subunits Are Differentially Regulated on a Post-transcriptional Level J. Biol. Chem., February 22, 2008; 283(8): 4578 - 4587. [Abstract] [Full Text] [PDF] S. J. Romney, C. Thacker, and E. A. 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