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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2571-2576. Prepublished online as a Blood First Edition Paper on November 16, 2004; DOI 10.1182/blood-2004-04-1566. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1566v1 105/6/2571    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 Zhou, S. Articles by Sorrentino, B. P. Search for Related Content PubMed PubMed Citation Articles by Zhou, S. Articles by Sorrentino, B. P. Related Collections Hematopoiesis and Stem Cells Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Increased expression of the Abcg2 transporter during erythroid maturation plays a role in decreasing cellular protoporphyrin IX levels Sheng Zhou, Yang Zong, Paul A. Ney, Geeta Nair, Clinton F. Stewart, and Brian P. Sorrentino From the Division of Experimental Hematology, the Department of Hematology/Oncology, the Department of Biochemistry, and the Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN. ABCG2/BCRP is a member of the adenosine triphosphate–binding cassette (ABC) transporter family and is expressed in intestine, kidney, and liver, where it modulates the absorption and excretion of xenobiotic compounds. ABCG2 is also expressed in hematopoietic stem cells and erythroid cells; however, little is known regarding its role in hematopoiesis. Abcg2 null mice have increased levels of protoporphyrin IX (PPIX) in erythroid cells, yet the mechanism for this remains uncertain. We have found that Abcg2 mRNA expression was up-regulated in differentiating erythroid cells, coinciding with increased expression of other erythroid-specific genes. This expression pattern was associated with significant amounts of ABCG2 protein on the membrane of mature peripheral blood erythrocytes. Erythroid cells engineered to express ABCG2 had significantly lower intracellular levels of PPIX, suggesting the modulation of PPIX level by ABCG2. This modulating activity was abrogated by treatment with a specific ABCG2 inhibitor, Ko143, implying that PPIX may be a direct substrate for the transporter. Taken together, our results demonstrate that ABCG2 plays a role in regulating PPIX levels during erythroid differentiation and suggest a potential role for ABCG2 as a genetic determinant in erythropoietic protoporphyria. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. van de Ven, R. Oerlemans, J. W. van der Heijden, G. L. Scheffer, T. D. de Gruijl, G. Jansen, and R. J. Scheper ABC drug transporters and immunity: novel therapeutic targets in autoimmunity and cancer J. Leukoc. Biol., November 1, 2009; 86(5): 1075 - 1087. [Abstract] [Full Text] [PDF] Y. Zong, S. Zhou, S. Fatima, and B. P. Sorrentino Expression of Mouse Abcg2 mRNA during Hematopoiesis Is Regulated by Alternative Use of Multiple Leader Exons and Promoters J. Biol. Chem., October 6, 2006; 281(40): 29625 - 29632. [Abstract] [Full Text] [PDF] A. Tamura, M. Watanabe, H. Saito, H. Nakagawa, T. Kamachi, I. Okura, and T. Ishikawa Functional Validation of the Genetic Polymorphisms of Human ATP-Binding Cassette (ABC) Transporter ABCG2: Identification of Alleles That Are Defective in Porphyrin Transport Mol. Pharmacol., July 1, 2006; 70(1): 287 - 296. [Abstract] [Full Text] [PDF]

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