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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1728-1735. Prepublished online as a Blood First Edition Paper on October 5, 2006; DOI 10.1182/blood-2006-04-018630. This Article Full Text Full Text (PDF) Supplemental Appendix and Figures Erratum (v109,p2735) All Versions of this Article: blood-2006-04-018630v1 109/4/1728    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 Joiner, C. H. Articles by Franco, R. S. Search for Related Content PubMed PubMed Citation Articles by Joiner, C. H. Articles by Franco, R. S. Related Collections Red Cells Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Urea stimulation of KCl cotransport induces abnormal volume reduction in sickle reticulocytes Clinton H. Joiner1,2, R. Kirk Rettig1,2, Maorong Jiang1,2, Mary Risinger1,2, and Robert S. Franco1,3 1 Cincinnati Comprehensive Sickle Cell Center, Division of Hematology/Oncology, University of Cincinnati College of Medicine, OH; 2 Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, OH; 3 Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, OH KCl cotransport (KCC) activity contributes to pathologic dehydration in sickle (SS) red blood cells (RBCs). KCC activation by urea was measured in SS and normal (AA) RBCs as Cl-dependent Rb influx. KCC-mediated volume reduction was assessed by measuring reticulocyte cellular hemoglobin concentration (CHC) cytometrically. Urea activated KCC fluxes in fresh RBCs to levels seen in swollen cells, although SS RBCs required lower urea concentrations than did normal (AA) RBCs. Little additional KCC stimulation by urea occurred in swollen AA or SS RBCs. The pH dependence of KCC in "euvolemic" SS RBCs treated with urea was similar to that in swollen cells. Urea triggered volume reduction in SS and AA reticulocytes, establishing a higher CHC. Volume reduction was Cl dependent and was limited by the KCC inhibitor, dihydro-indenyl-oxyalkanoic acid. Final CHC depended on urea concentration, but not on initial CHC. Under all activation conditions, volume reduction was exaggerated in SS reticulocytes and produced higher CHCs than in AA reticulocytes. The sulfhydryl-reducing agent, dithiothreitol, normalized the sensitivity of KCC activation to urea in SS RBCs and mitigated the urea-stimulated volume decrease in SS reticulocytes, suggesting that the dysfunctional activity of KCC in SS RBCs was due in part to reversible sulfhydryl oxidation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Iolascon, L. De Falco, F. Borgese, M. R. Esposito, R. A. Avvisati, P. Izzo, C. Piscopo, H. Guizouarn, A. Biondani, A. Pantaleo, et al. A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis Haematologica, August 1, 2009; 94(8): 1049 - 1059. [Abstract] [Full Text] [PDF] M. Risinger, J. Rinehart, S. Crable, A. Ottlinger, R. Winkelmann, D. Pan, C. Huebner, P. G. Gallagher, and C. H. Joiner Structural and Functional Interactions of KCl Cotransport Proteins KCC1 and KCC3 in Sickle and Normal Erythrocyte Membranes Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 2474 - 2474. [Abstract] C. H. Joiner Gardos pathway to sickle cell therapies? Blood, April 15, 2008; 111(8): 3918 - 3919. [Full Text] [PDF]

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