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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2864-2871. Prepublished online as a Blood First Edition Paper on July 9, 2007; DOI 10.1182/blood-2007-01-065201. This Article Full Text (PDF) All Versions of this Article: blood-2007-01-065201v1 110/8/2864    most recent Alert me when this article is cited Alert me if a correction is posted 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 Aerbajinai, W. Articles by Rodgers, G. P Search for Related Content PubMed PubMed Citation Articles by Aerbajinai, W. Articles by Rodgers, G. P Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 3, 2007 Accepted June 22, 2007 Thalidomide induces -globin gene expression through increased reactive oxygen species-mediated p38 MAPK signaling and histone H4 acetylation in adult erythropoiesis Wulin Aerbajinai, Jianqiong Zhu, Zhigang Gao, Kyung Chin, and Griffin P Rodgers* Molecular and Clinical Hematology Branch, National Institute of Diabetes, Digestive and Kidney Diseases/NIH, Bethesda, MD, United States * Corresponding author; email: gr5n{at}nih.gov. Although thalidomide has been shown to improve anemia in some patients with myelodysplastic syndromes and stimulates erythropoietin in multiple myeloma patients, thalidomide's specific effects on -globin gene expression during erythroid differentiation has not been studied. Here, we investigated the effects of thalidomide on -globin gene expression and the involved signaling pathway using an ex vivo culture system of primary human CD34+ cells. We found that thalidomide induced -globin mRNA expression in a dose-dependent manner, but had no effect on --globin expression. We also demonstrated that intracellular reactive oxygen species (ROS) levels were increased by treatment with thalidomide for 48 h (from day 3 to day 5). Western blot analysis demonstrated that thalidomide activated the p38 mitogen-activated protein kinase (MAPK) signaling pathway in a time- and dose-dependent manner and increased histone H4 acetylation. Pretreatment of cells with the anti-oxidant enzyme catalase and the intracellular hydroxyl scavenger dimethylthiourea (DMTU) abrogated the thalidomide-induced p38 MAPK activation and histone H4 acetylation. Moreover, pretreatment with catalase and DMTU diminished thalidomide-induced -globin gene expression. These data indicate that thalidomide induces increased expression of the -globin gene via ROS-dependent activation of the p38 MAPK signaling pathway and histone H4 acetylation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: THAL for THAL? David H. K. Chui Blood 2007 110: 2788-2789. [Full Text] [PDF] This article has been cited by other articles: H. Bhatia, J. L. Hallock, A. Dutta, S. Karkashon, L. S. Sterner, T. Miyazaki, A. Dean, and J. A. Little Short-chain fatty acid-mediated effects on erythropoiesis in primary definitive erythroid cells Blood, June 18, 2009; 113(25): 6440 - 6448. [Abstract] [Full Text] [PDF] R. S. Al-Lamki, J. Wang, A. M. Tolkovsky, J. A. Bradley, J. L. Griffin, S. Thiru, E. C.Y. Wang, E. Bolton, W. Min, P. Moore, et al. TL1A Both Promotes and Protects from Renal Inflammation and Injury J. Am. Soc. Nephrol., May 1, 2008; 19(5): 953 - 960. [Abstract] [Full Text] [PDF]

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