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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2565-2573. Prepublished online as a Blood First Edition Paper on June 17, 2004; DOI 10.1182/blood-2003-11-3858. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-11-3858v1 104/8/2565    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 Friedman, J. S. Articles by Burakoff, S. J. Search for Related Content PubMed PubMed Citation Articles by Friedman, J. S. Articles by Burakoff, S. J. Related Collections Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS SOD2-deficiency anemia: protein oxidation and altered protein expression reveal targets of damage, stress response, and antioxidant responsiveness Jeffrey S. Friedman, Mary F. Lopez, Mark D. Fleming, Alicia Rivera, Florent M. Martin, Megan L. Welsh, Ashleigh Boyd, Susan R. Doctrow, and Steven J. Burakoff From the Scripps Research Institute, La Jolla, CA; Perkin-Elmer Life and Analytical Sciences, Boston, MA; Children's Hospital, Boston, MA; Eukarion Inc, Bedford, MA; the Skirball Institute and NYU School of Medicine, New York, NY; and Oxford University, Oxford, United Kingdom. SOD2 is an antioxidant protein that protects cells against mitochondrial superoxide. Hematopoietic stem cells (HSCs) lacking SOD2 are capable of rescuing lethally irradiated hosts, but reconstituted animals display a persistent hemolytic anemia characterized by increased oxidative damage to red cells, with morphologic similarity to human "sideroblastic" anemia. We report further characterization of this novel SOD2-deficiency anemia. Electron micrographs of SOD2-deficient reticulocytes reveal striking mitochondrial proliferation and mitochondrial membrane thickening. Peripheral blood smears show abundant iron-stainable granules in mature red cells (siderocytes). Fluorescence-activated cell sorting (FACS) analysis of cells labeled with oxidation-sensitive dyes demonstrates enhanced production of superoxide and hydrogen peroxide by SOD2-deficient cells. Oxidative damage to proteins is increased in SOD2-deficient cells, with much of the damage affecting membrane/insoluble proteins. Red cell proteome analysis demonstrates that several proteins involved in folding/chaperone function, redox regulation, adenosine triphosphate (ATP) synthesis, and red cell metabolism show altered expression in SOD2-deficient cells. This data, combined with information on how protein expression levels change upon antioxidant therapy, will aid in identification of proteins that are sensitive to oxidative damage in this model, and by extension, may have a role in the regulation of red cell lifespan in other hemolytic disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Elorza, B. Hyde, H. K. Mikkola, S. Collins, and O. S. Shirihai UCP2 Modulates Cell Proliferation through the MAPK/ERK Pathway during Erythropoiesis and Has No Effect on Heme Biosynthesis J. Biol. Chem., November 7, 2008; 283(45): 30461 - 30470. [Abstract] [Full Text] [PDF] C. Pondarre, D. R. Campagna, B. Antiochos, L. Sikorski, H. Mulhern, and M. D. Fleming Abcb7, the gene responsible for X-linked sideroblastic anemia with ataxia, is essential for hematopoiesis Blood, April 15, 2007; 109(8): 3567 - 3569. [Abstract] [Full Text] [PDF] P. Cavadini, G. Biasiotto, M. Poli, S. Levi, R. Verardi, I. Zanella, M. Derosas, R. Ingrassia, M. Corrado, and P. Arosio RNA silencing of the mitochondrial ABCB7 transporter in HeLa cells causes an iron-deficient phenotype with mitochondrial iron overload Blood, April 15, 2007; 109(8): 3552 - 3559. [Abstract] [Full Text] [PDF] C. L. Limoli, E. Giedzinski, J. Baure, S. R. Doctrow, R. Rola, and J. R. Fike Using superoxide dismutase/catalase mimetics to manipulate the redox environment of neural precursor cells Radiat Prot Dosimetry, December 1, 2006; 122(1-4): 228 - 236. [Abstract] [Full Text] [PDF] K. J. Morten, B. A. C. Ackrell, and S. Melov Mitochondrial Reactive Oxygen Species in Mice Lacking Superoxide Dismutase 2: ATTENUATION VIA ANTIOXIDANT TREATMENT J. Biol. Chem., February 10, 2006; 281(6): 3354 - 3359. [Abstract] [Full Text] [PDF]

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