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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1857-1863. Prepublished online as a Blood First Edition Paper on May 17, 2005; DOI 10.1182/blood-2004-11-4344. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-11-4344v1 106/5/1857    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 Rhodes, M. M. Articles by Koury, M. J. Search for Related Content PubMed PubMed Citation Articles by Rhodes, M. M. Articles by Koury, M. J. Related Collections Apoptosis Hematopoiesis Red Cells Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Bcl-xL prevents apoptosis of late-stage erythroblasts but does not mediate the antiapoptotic effect of erythropoietin Melissa M. Rhodes, Prapaporn Kopsombut, Maurice C. Bondurant, James O. Price, and Mark J. Koury From the Departments of Pediatrics, Medicine, and Pathology, Vanderbilt University Medical Center and Tennessee Valley Healthcare System VA Medical Center, Nashville, TN The long form of B-cell lymphoma-x (Bcl-xL), an outer mitochondrial membrane protein, has been proposed to mediate the antiapoptotic action of erythropoietin on erythroid progenitor cells and to be necessary for heme synthesis in erythroblasts. Mice with conditional knockout of Bcl-xL (conditional bcl-x-/- mice) develop severe anemia that has been attributed to hemolysis and is accompanied by splenomegaly. We characterized further the anemia of conditional bcl-x-/- mice and investigated the role of Bcl-xL in the action of erythropoietin and in heme synthesis. We analyzed peripheral blood cells and cultured splenic erythroblasts of conditional bcl-x-/- mice and littermates that were rendered anemic by bleeding. Although they had massive splenic erythroblastosis, conditional bcl-x-/- mice had decreased circulating reticulocytes compared to littermates even prior to bleeding the littermates. Compared to erythroblasts of bled littermates, bcl-x-/- erythroblasts cultured with erythropoietin underwent apoptosis during the later, hemoglobin-synthesizing stages of differentiation. The bcl-x-/- erythroblasts synthesized heme, but at reduced rates compared to bled littermate erythroblasts. When cultured without erythropoietin, bcl-x-/- erythroblasts underwent apoptosis at early stages of differentiation, prior to hemoglobin synthesis. Bcl-xL is not required for heme synthesis and does not mediate the antiapoptotic effects of erythropoietin, but it prevents ineffective erythropoiesis due to apoptosis in late-stage, hemoglobin-synthesizing erythroblasts. (Blood. 2005;106:1857-1863) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Erythroid Bcl-xL: better late than never Jeffery L. Miller Blood 2005 106: 1515-1516. [Full Text] [PDF] This article has been cited by other articles: P. Sathyanarayana, A. Dev, J. Fang, E. Houde, O. Bogacheva, O. Bogachev, M. Menon, S. Browne, A. Pradeep, C. Emerson, et al. EPO receptor circuits for primary erythroblast survival Blood, June 1, 2008; 111(11): 5390 - 5399. [Abstract] [Full Text] [PDF] A. R. Gordon, S. V. Outram, M. Keramatipour, C. A. Goddard, W. H. Colledge, J. C. Metcalfe, A. L. Hager-Theodorides, T. Crompton, and P. R. Kemp Splenomegaly and Modified Erythropoiesis in KLF13-/- Mice J. Biol. 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Yamamoto GATA-4 Incompletely Substitutes for GATA-1 in Promoting Both Primitive and Definitive Erythropoiesis in Vivo J. Biol. Chem., October 27, 2006; 281(43): 32820 - 32830. [Abstract] [Full Text] [PDF] M. P. Menon, J. Fang, and D. M. Wojchowski Core erythropoietin receptor signals for late erythroblast development Blood, April 1, 2006; 107(7): 2662 - 2672. [Abstract] [Full Text] [PDF]

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