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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1917-1922. Prepublished online as a Blood First Edition Paper on October 19, 2006; DOI 10.1182/blood-2006-08-044172. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-08-044172v1 109/5/1917    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 Zou, G.-M. Articles by Yoder, M. C. Search for Related Content PubMed PubMed Citation Articles by Zou, G.-M. Articles by Yoder, M. C. Related Collections Hematopoiesis and Stem Cells Gene Expression Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Ape1 regulates hematopoietic differentiation of embryonic stem cells through its redox functional domain Gang-Ming Zou1,2, Mei-Hua Luo1,2, April Reed1, Mark R. Kelley1,4, and Mervin C. Yoder1,2,4 1 Department of Pediatrics (Section of Hematology/Oncology), 2 Herman B. Wells Center for Pediatric Research, 3 Department of Pharmacology and Toxicology, and 4 Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis Ape1 is a molecule with dual functions in DNA repair and redox regulation of transcription factors. In Ape1-deficient mice, embryos do not survive beyond embryonic day 9, indicating that this molecule is required for normal embryo development. Currently, direct evidence of the role of Ape1 in regulating hematopoiesis is lacking. We used the embryonic stem (ES) cell differentiation system and an siRNA approach to knockdown Ape1 gene expression to test the role of Ape1 in hematopoiesis. Hemangioblast development from ES cells was reduced 2- to 3-fold when Ape1 gene expression was knocked down by Ape1-specific siRNA, as was primitive and definitive hematopoiesis. Impaired hematopoiesis was not associated with increased apoptosis in siRNA-treated cells. To begin to explore the mechanism whereby Ape1 regulates hematopoiesis, we found that inhibition of the redox activity of Ape1 with E3330, a specific Ape1 redox inhibitor, but not Ape1 DNA repair activity, which was blocked using the small molecule methoxyamine, affected cytokine-mediated hemangioblast development in vitro. In summary, these data indicate Ape1 is required in normal embryonic hematopoiesis and that the redox function, but not the repair endonuclease activity, of Ape1 is critical in normal embryonic hematopoietic development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. D. Curtis, D. L. Thorngren, Y. S. Ziegler, A. Sarkeshik, J. R. Yates, and A. M. Nardulli Apurinic/Apyrimidinic Endonuclease 1 Alters Estrogen Receptor Activity and Estrogen-Responsive Gene Expression Mol. Endocrinol., September 1, 2009; 23(9): 1346 - 1359. [Abstract] [Full Text] [PDF] G.-M. Zou and A. Maitra Small-molecule inhibitor of the AP endonuclease 1/REF-1 E3330 inhibits pancreatic cancer cell growth and migration Mol. Cancer Ther., July 1, 2008; 7(7): 2012 - 2021. [Abstract] [Full Text] [PDF] R. L. Maher and L. B. Bloom Pre-steady-state Kinetic Characterization of the AP Endonuclease Activity of Human AP Endonuclease 1 J. Biol. Chem., October 19, 2007; 282(42): 30577 - 30585. [Abstract] [Full Text] [PDF]

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