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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4051-4060. Prepublished online as a Blood First Edition Paper on August 28, 2008; DOI 10.1182/blood-2008-05-158535. This Article Full Text (PDF) All Versions of this Article: blood-2008-05-158535v1 112/10/4051    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 O'Brien, J. J Articles by Phipps, R. P Search for Related Content PubMed PubMed Citation Articles by O'Brien, J. J Articles by Phipps, R. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 22, 2008 Accepted August 2, 2008 15-deoxy-12,14-PGJ2 enhances platelet production from megakaryocytes Jamie J O'Brien, Sherry L Spinelli, Joanna Tober, Neil Blumberg, Charles W Francis, Mark B Taubman, James Palis, Kathryn E Seweryniak, Jacqueline M Gertz, and Richard P Phipps* Environmental Medicine and the Lung Biology and Disease Program, University of Rochester, Rochester, New York, United States Pathology and Laboratory Medicine, University of Rochester, Rochester, New York, United States Center for Pediatric Biomedical Research, Univeristy of Rochester, Rochester, New York, United States Medicine, University of Rochester, Rochester, New York, United States Department of Pediatrics, University of Rochester, Rochester, New York, United States * Corresponding author; email: richard_phipps{at}urmc.rochester.edu. Thrombocytopenia is a critical problem that occurs in many hematological diseases, as well as after cancer therapy and radiation exposure. Platelet transfusion is the most commonly used therapy, but has limitations of alloimmunization, availability, and expense. Thus, the development of safe, small molecules to enhance platelet production would be advantageous for the treatment of thrombocytopenia. Herein, we report that an important lipid mediator and a PPAR ligand called 15-deoxy-12,14 prostaglandin J2 (15d-PGJ2), increases Meg-01 maturation and platelet production. 15d-PGJ2 also promotes platelet formation from culture-derived mouse and human megakaryocytes and accelerates platelet recovery after in vivo radiation-induced bone marrow injury. Interestingly, the platelet-enhancing effects of 15d-PGJ2 in Meg-01 cells are independent of PPAR, but dependent on reactive oxygen species (ROS) accumulation; treatment with antioxidants such as glutathione ethyl ester (GSH-EE) or N-acetylcysteine (NAC) attenuate 15d-PGJ2-induced platelet production. Collectively, these data support the concept that megakaryocyte redox status plays an important role in platelet generation and that small electrophilic molecules may have clinical efficacy for improving platelet numbers in thrombocytopenic patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. J. Bernard, K. E. Seweryniak, A. D. Koniski, S. L. Spinelli, N. Blumberg, C. W. Francis, M. B. Taubman, J. Palis, and R. P. Phipps Foxp3 Regulates Megakaryopoiesis and Platelet Function Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1874 - 1882. [Abstract] [Full Text] [PDF] D. J. Hilton, B. T. Kile, and W. S. Alexander Mutational inhibition of c-Myb or p300 ameliorates treatment-induced thrombocytopenia Blood, May 28, 2009; 113(22): 5599 - 5604. [Abstract] [Full Text] [PDF]

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