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Effect of polyamines on hemoglobin and globin chain synthesis
Authors:S K Ballas  E D Smith  L J Marton
Institution:1. Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 USA;2. Department of Laboratory Medicine, University of California, San Francisco, California 94143 USA;1. Institute of Cardiovascular Sciences, Level 1 IBR, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK;2. Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, The Midlands, UK;3. Biodiscovery Institute, University Park, University of Nottingham, Nottingham, UK;4. Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands;5. Department of Cardiology, University Hospitals Birmingham, Birmingham, UK;1. Laboratory for Advanced Genomics, Department of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia;2. The Mina & Everard Goodman Faculty of Life Sciences and Institute of Nanotechnology, Bar-Ilan University, Ramat Gan 52900, Israel;1. Center for Benign Hematology, Thrombosis and Hemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands;2. Central Diagnostic Laboratory, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands;3. Department of Internal Medicine (Hematology), St. Antonius Hospital, Utrecht, the Netherlands;4. Department of Internal Medicine (Hematology), Meander Medical Center, Amersfoort, the Netherlands;5. Department of Internal Medicine (Hematology), Diakonessenhuis Utrecht, Utrecht, the Netherlands;6. Department of Internal Medicine (Hematology), Slingeland Ziekenhuis, Doetinchem, the Netherlands;1. Department of Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA;2. Department of Pharmacology, Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA;3. Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA;4. Proteomics and Metabolomics Core Facility, Weill Cornell Medicine, New York, NY 10065, USA
Abstract:Exposure of reticulocytes to 25 mM spermidine and spermine stimulates the incorporation of 14C leucine into hemoglobin and globin polypeptide chains. These two polyamines stimulate beta chain synthesis to a greater extent than they stimulate alpha chain synthesis, thus resulting in a decreased synthetic alpha/beta globin ratio. Because of the low permeability of the red cell membrane to these polycations, less than 1.0% of extracellular spermidine and spermine accumulate within the erythrocyte, thus these effects occur at intracellular polyamine levels that are physiological. Putrescine progressively decreases hemoglobin synthesis at extracellular concentrations greater than 10 mM without affecting the synthetic alpha/beta ratio. These findings suggest a role for polyamines in the fine tuning of the alpha/beta globin ratio at the translational level.
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