SEARCH:   Advanced

Blood, 1 February 2008, Vol. 111, No. 3, pp. 1690-1699. Prepublished online as a Blood First Edition Paper on November 1, 2007; DOI 10.1182/blood-2007-07-102335. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-07-102335v1 111/3/1690    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 Sohn, Y.-S. Articles by Cabantchik, Z. I. Search for Related Content PubMed PubMed Citation Articles by Sohn, Y.-S. Articles by Cabantchik, Z. I. Related Collections Red Cells Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Redistribution of accumulated cell iron: a modality of chelation with therapeutic implications Yang-Sung Sohn1, William Breuer1, Arnold Munnich2, and Z. Ioav Cabantchik1 1 Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Safra Campus at Givat Ram, Jerusalem, Israel; and 2 Clinical Research Unit, Medical Genetic Clinic and Research Unit, Inserm Unite 781, Hôpital Necker-Enfants-Malades and Université Paris V René Descartes, Paris, France Various pathologies are characterized by the accumulation of toxic iron in cell compartments. In anemia of chronic disease, iron is withheld by macrophages, leaving extracellular fluids iron-depleted. In Friedreich ataxia, iron levels rise in the mitochondria of excitable cells but decrease in the cytosol. We explored the possibility of using deferiprone, a membrane-permeant iron chelator in clinical use, to capture labile iron accumulated in specific organelles of cardiomyocytes and macrophages and convey it to other locations for physiologic reuse. Deferiprone's capacity for shuttling iron between cellular organelles was assessed with organelle-targeted fluorescent iron sensors in conjunction with time-lapse fluorescence microscopy imaging. Deferiprone facilitated transfer of iron from extracellular media into nuclei and mitochondria, from nuclei to mitochondria, from endosomes to nuclei, and from intracellular compartments to extracellular apotransferrin. Furthermore, it mobilized iron from iron-loaded cells and donated it to preerythroid cells for hemoglobin synthesis, both in the presence and in the absence of transferrin. These unique properties of deferiprone underlie mechanistically its capacity to alleviate iron accumulation in dentate nuclei of Friedreich ataxia patients and to donate tissue-chelated iron to plasma transferrin in thalassemia intermedia patients. Deferiprone's shuttling properties could be exploited clinically for treating diseases involving regional iron accumulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Iron caught on the shuttle Günter Weiss Blood 2008 111: 980. [Full Text] [PDF] This article has been cited by other articles: K. Li, E. K. Besse, D. Ha, G. Kovtunovych, and T. A. Rouault Iron-dependent regulation of frataxin expression: implications for treatment of Friedreich ataxia Hum. Mol. Genet., August 1, 2008; 17(15): 2265 - 2273. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020