SEARCH:   Advanced

Blood, 1 October 2005, Vol. 106, No. 7, pp. 2580-2589. Prepublished online as a Blood First Edition Paper on June 14, 2005; DOI 10.1182/blood-2005-04-1365. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-04-1365v1 106/7/2580    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Galy, B. Articles by Hentze, M. W. Search for Related Content PubMed PubMed Citation Articles by Galy, B. Articles by Hentze, M. W. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2) Bruno Galy, Dunja Ferring, Belen Minana, Oliver Bell, Heinz G. Janser, Martina Muckenthaler, Klaus Schümann, and Matthias W. Hentze From the European Molecular Biology Laboratory, Heidelberg, Germany; Institut für Pharmakologie und Toxikologie der Ludwig-Maximilians-Universität, München, Germany; and Lehrstuhl für Ernährungphysiologie, Technical University, München, Germany. Iron regulatory protein 2 (IRP2)-deficient mice have been reported to suffer from late-onset neurodegeneration by an unknown mechanism. We report that young adult Irp2-/- mice display signs of iron mismanagement within the central iron recycling pathway in the mammalian body, the liver-bone marrow-spleen axis, with altered body iron distribution and compromised hematopoiesis. In comparison with wild-type littermates, Irp2-/- mice are mildly microcytic with reduced serum hemoglobin levels and hematocrit. Serum iron and transferrin saturation are unchanged, and hence microcytosis is not due to an overt decrease in systemic iron availability. The liver and duodenum are iron loaded, while the spleen is iron deficient, associated with a reduced expression of the iron exporter ferroportin. A reduction in transferrin receptor 1 (TfR1) mRNA levels in the bone marrow of Irp2-/- mice can plausibly explain the microcytosis by an intrinsic defect in erythropoiesis due to a failure to adequately protect TfR1 mRNA against degradation. This study links a classic regulator of cellular iron metabolism to systemic iron homeostasis and erythropoietic TfR1 expression. Furthermore, this work uncovers aspects of mammalian iron metabolism that can or cannot be compensated for by the expression of IRP1. (Blood. 2005;106: 2580-2589) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Khomenko, S. Szabo, X. Deng, H. Ishikawa, G. J. Anderson, and G. D. McLaren Role of iron in the pathogenesis of cysteamine-induced duodenal ulceration in rats Am J Physiol Gastrointest Liver Physiol, June 1, 2009; 296(6): G1277 - G1286. [Abstract] [Full Text] [PDF] J.-F. Briat, K. Ravet, N. Arnaud, C. Duc, J. Boucherez, B. Touraine, F. Cellier, and F. Gaymard New insights into ferritin synthesis and function highlight a link between iron homeostasis and oxidative stress in plants Ann. Bot., May 29, 2009; (2009) mcp128v1. [Abstract] [Full Text] [PDF] K. B. Zumbrennen, M. L. Wallander, S. J. Romney, and E. A. Leibold Cysteine Oxidation Regulates the RNA-Binding Activity of Iron Regulatory Protein 2 Mol. Cell. Biol., April 15, 2009; 29(8): 2219 - 2229. [Abstract] [Full Text] [PDF] A. Iolascon, L. De Falco, and C. Beaumont Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis Haematologica, March 1, 2009; 94(3): 395 - 408. [Abstract] [Full Text] [PDF] D. Ferring-Appel, M. W. Hentze, and B. Galy Cell-autonomous and systemic context-dependent functions of iron regulatory protein 2 in mammalian iron metabolism Blood, January 15, 2009; 113(3): 679 - 687. [Abstract] [Full Text] [PDF] M. C. D'Anna, T. V. Veuthey, and M. E. Roque Immunolocalization of Ferroportin in Healthy and Anemic Mice J. Histochem. Cytochem., January 1, 2009; 57(1): 9 - 16. [Abstract] [Full Text] [PDF] M. A. Kerenyi, F. Grebien, H. Gehart, M. Schifrer, M. Artaker, B. Kovacic, H. Beug, R. Moriggl, and E. W. Mullner Stat5 regulates cellular iron uptake of erythroid cells via IRP-2 and TfR-1 Blood, November 1, 2008; 112(9): 3878 - 3888. [Abstract] [Full Text] [PDF] M. L. Wallander, K. B. Zumbrennen, E. S. Rodansky, S. J. Romney, and E. A. Leibold Iron-independent Phosphorylation of Iron Regulatory Protein 2 Regulates Ferritin during the Cell Cycle J. Biol. Chem., August 29, 2008; 283(35): 23589 - 23598. [Abstract] [Full Text] [PDF] M. C. Ghosh, W.-H. Tong, D. Zhang, H. Ollivierre-Wilson, A. Singh, M. C. Krishna, J. B. Mitchell, and T. A. Rouault Tempol-mediated activation of latent iron regulatory protein activity prevents symptoms of neurodegenerative disease in IRP2 knockout mice PNAS, August 19, 2008; 105(33): 12028 - 12033. [Abstract] [Full Text] [PDF] N. C. Andrews Forging a field: the golden age of iron biology Blood, July 15, 2008; 112(2): 219 - 230. [Full Text] [PDF] F. Missirlis, S. Kosmidis, T. Brody, M. Mavrakis, S. Holmberg, W. F. Odenwald, E. M. C. Skoulakis, and T. A. Rouault Homeostatic Mechanisms for Iron Storage Revealed by Genetic Manipulations and Live Imaging of Drosophila Ferritin Genetics, September 1, 2007; 177(1): 89 - 100. [Abstract] [Full Text] [PDF] W. Wang, X. Di, R. B. D'Agostino Jr., S. V. Torti, and F. M. Torti Excess Capacity of the Iron Regulatory Protein System J. Biol. Chem., August 24, 2007; 282(34): 24650 - 24659. [Abstract] [Full Text] [PDF] C. Beaumont Heme/Fe-S intimacies make RBCs blush Blood, August 15, 2007; 110(4): 1085 - 1086. [Full Text] [PDF] C. Camaschella, A. Campanella, L. De Falco, L. Boschetto, R. Merlini, L. Silvestri, S. Levi, and A. Iolascon The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload Blood, August 15, 2007; 110(4): 1353 - 1358. [Abstract] [Full Text] [PDF] J. Wang, C. Fillebeen, G. Chen, A. Biederbick, R. Lill, and K. Pantopoulos Iron-Dependent Degradation of Apo-IRP1 by the Ubiquitin-Proteasome Pathway Mol. Cell. Biol., April 1, 2007; 27(7): 2423 - 2430. [Abstract] [Full Text] [PDF] D. Zhang, E. Meyron-Holtz, and T. A. Rouault Renal Iron Metabolism: Transferrin Iron Delivery and the Role of Iron Regulatory Proteins J. Am. Soc. Nephrol., February 1, 2007; 18(2): 401 - 406. [Full Text] [PDF] M. Sanchez, B. Galy, T. Dandekar, P. Bengert, Y. Vainshtein, J. Stolte, M. U. Muckenthaler, and M. W. Hentze Iron Regulation and the Cell Cycle: IDENTIFICATION OF AN IRON-RESPONSIVE ELEMENT IN THE 3'-UNTRANSLATED REGION OF HUMAN CELL DIVISION CYCLE 14A mRNA BY A REFINED MICROARRAY-BASED SCREENING STRATEGY J. Biol. Chem., August 11, 2006; 281(32): 22865 - 22874. [Abstract] [Full Text] [PDF] M. Schranzhofer, M. Schifrer, J. A. Cabrera, S. Kopp, P. Chiba, H. Beug, and E. W. Mullner Remodeling the regulation of iron metabolism during erythroid differentiation to ensure efficient heme biosynthesis Blood, May 15, 2006; 107(10): 4159 - 4167. [Abstract] [Full Text] [PDF] J. Wang, C. Fillebeen, G. Chen, B. Andriopoulos, and K. Pantopoulos Sodium Nitroprusside Promotes IRP2 Degradation via an Increase in Intracellular Iron and in the Absence of S Nitrosylation at C178. Mol. Cell. Biol., March 1, 2006; 26(5): 1948 - 1954. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020