Skip to content
University of Maryland LibrariesDigital Repository at the University of Maryland
    • Login
    View Item 
    •   DRUM
    • Theses and Dissertations from UMD
    • UMD Theses and Dissertations
    • View Item
    •   DRUM
    • Theses and Dissertations from UMD
    • UMD Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    SITE-SPECIFIC INTERACTION OF DOXORUBICIN IN THE IRON RESPONSIVE ELEMENT RNA: IMPLICATIONS IN CELLULAR IRON HOMEOSTASIS AND NON-IRON DEFICIENCY ANEMIA

    Thumbnail
    View/Open
    Alvarado_umd_0117E_14912.pdf (5.560Mb)
    No. of downloads: 532

    Date
    2014
    Author
    Alvarado, Luigi Jhon
    Advisor
    Dayie, Theodore K
    Metadata
    Show full item record
    Abstract
    A widely utilized chemotherapy drug, doxorubicin, has recently been shown to bind to a mammalian 5′ untranslated region Iron Responsive Element (IRE) RNA. In conjunction with the Iron Regulatory Protein (IRP), IRE RNA is involved in cellular iron homeostasis at the translational level. This tight RNA/protein complex prevents ribosomal assembly, hindering translation initiation of iron storage proteins, e.g. ferritin, under low cellular iron conditions. Conversely, iron overload is conducive to complex dissociation, allowing for up-regulation of the same proteins. However, this system is not entirely efficient. Some anemic patients receive adjuvant chelation therapies upon chronic blood transfusions to sequester excess labile iron. The use of doxorubicin to promote RNA/protein dissociation could potentially allow for downstream up-regulation of ferritin. In this work, I show how doxorubicin interacts with IRE RNA using multidimensional nuclear magnetic resonance, fluorescence spectroscopy, and electrophoretic mobility shift assays. All three approaches converge on the observation that the IRE/IRP complex formation is disrupted by doxorubicin. Obtaining further data on the RNA/protein/drug interactions may lead to unveiling a validated RNA target as a complementary treatment of iron overload disease, e.g. sickle cell anemia.
    URI
    http://hdl.handle.net/1903/15143
    Collections
    • Chemistry & Biochemistry Theses and Dissertations
    • UMD Theses and Dissertations

    DRUM is brought to you by the University of Maryland Libraries
    University of Maryland, College Park, MD 20742-7011 (301)314-1328.
    Please send us your comments.
    Web Accessibility
     

     

    Browse

    All of DRUMCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    LoginRegister
    Pages
    About DRUMAbout Download Statistics

    DRUM is brought to you by the University of Maryland Libraries
    University of Maryland, College Park, MD 20742-7011 (301)314-1328.
    Please send us your comments.
    Web Accessibility