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Blood, 1 July 2005, Vol. 106, No. 1, pp. 75-85. Prepublished online as a Blood First Edition Paper on March 15, 2005; DOI 10.1182/blood-2004-08-3033. This Article Full Text (PDF) All Versions of this Article: 2004-08-3033v1 106/1/75    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 Zhang, X. Articles by Pang, Q. Search for Related Content PubMed PubMed Citation Articles by Zhang, X. Articles by Pang, Q. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 6, 2004 Accepted March 9, 2005 Hypoxia-reoxygenation induces premature senescence in FA bone marrow hematopoietic cells Xiaoling Zhang, June Li, Daniel P Sejas, and Qishen Pang* Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA * Corresponding author; email: qishen.pang{at}cchmc.org. Hematopoietic cells are often exposed to transient hypoxia and reoxygenation as they develop and migrate. Given bone marrow (BM) failure occurred in patients with Fanconi anemia (FA), we reason that hypoxia-then-reoxygenation represents a physiologically relevant stress for FA hematopoietic progenitor/stem cells. Here we show that expansion of Fancc-/- BM cells enriched for progenitor and stem cells was significantly decreased after two continuous cycles of hyperoxic-hypoxic-hyperoxic treatments compared to WT BM cells. This inhibition was attributable to a marked decrease of Lin-Scal- c-kit+ cells and more primitive Lin-Scal+ c-kit+ cells in Fancc-/- BM cells following reoxygenation. Evaluation of the cell cycle profile of long-term BM culture (LTBMC) revealed that a vast majority (70.6%) of reoxygenated Fancc-/- LTBMC cells was residing in the G0+G1 phases compared with 55.8% in WT LTBMC cells. Fancc-/- LTBMC cells stained intensely for SA--galactosidase activity, a biomarker for senescence; this was associated with increased expression of senescence-associated proteins p53 and p21WAF1/ CIP1. Taken together, these results suggest that reoxygenation induces premature senescence in Fancc-/- BM hematopoietic cells by signaling through p53, upregulating p21 and causing senescent cell cycle arrest. Thus, reoxygenation-induced premature senescence may be a novel mechanism underlying hematopoietic cell depletion and BM failure in FA. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Grillari, H. Katinger, and R. Voglauer Contributions of DNA interstrand cross-links to aging of cells and organisms Nucleic Acids Res., December 14, 2007; (2007) gkm1065v1. [Abstract] [Full Text] [PDF] X. Zhang, D. P. Sejas, Y. Qiu, D. A. Williams, and Q. Pang Inflammatory ROS promote and cooperate with the Fanconi anemia mutation for hematopoietic senescence J. Cell Sci., May 1, 2007; 120(9): 1572 - 1583. [Abstract] [Full Text] [PDF] S. S. Mukhopadhyay, K. S. Leung, M. J. Hicks, P. J. Hastings, H. Youssoufian, and S. E. Plon Defective mitochondrial peroxiredoxin-3 results in sensitivity to oxidative stress in Fanconi anemia J. Cell Biol., October 23, 2006; 175(2): 225 - 235. [Abstract] [Full Text] [PDF] J. Li, D. P. Sejas, R. Rani, T. Koretsky, G. C. Bagby, and Q. Pang Nucleophosmin Regulates Cell Cycle Progression and Stress Response in Hematopoietic Stem/Progenitor Cells J. Biol. Chem., June 16, 2006; 281(24): 16536 - 16545. [Abstract] [Full Text] [PDF]

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