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

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dc.contributor.advisorDayie, Theodore Ken_US
dc.contributor.authorAlvarado, Luigi Jhonen_US
dc.contributor.departmentBiochemistryen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2014-06-24T05:37:53Z
dc.date.available2014-06-24T05:37:53Z
dc.date.issued2014en_US
dc.description.abstractA 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.en_US
dc.identifier.urihttp://hdl.handle.net/1903/15143
dc.language.isoenen_US
dc.subject.pqcontrolledBiochemistryen_US
dc.subject.pqcontrolledBiophysicsen_US
dc.subject.pqcontrolledBiologyen_US
dc.subject.pquncontrolledAnemiaen_US
dc.subject.pquncontrolledFluorescence Spectroscopyen_US
dc.subject.pquncontrolledIron Regulatory Proteinen_US
dc.subject.pquncontrolledIron Responsive Element RNAen_US
dc.subject.pquncontrolledNuclear Magnetic Resonanceen_US
dc.titleSITE-SPECIFIC INTERACTION OF DOXORUBICIN IN THE IRON RESPONSIVE ELEMENT RNA: IMPLICATIONS IN CELLULAR IRON HOMEOSTASIS AND NON-IRON DEFICIENCY ANEMIAen_US
dc.typeDissertationen_US

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