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dc.contributor.advisorPetris, Michael J.eng
dc.contributor.authorWhite, Carine, 1976-eng
dc.date.issued2008eng
dc.date.submitted2008 Falleng
dc.descriptionTitle from PDF of title page (University of Missouri--Columbia, viewed on March 8, 2010).eng
dc.descriptionThe entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.eng
dc.descriptionDissertation advisor: Dr. Michael J. Petris.eng
dc.descriptionVita.eng
dc.descriptionPh. D. University of Missouri--Columbia 2008.eng
dc.description.abstractCopper is an essential cofactor of enzymes involved in a variety of important metabolic processes including ATP production, iron transport, and antioxidant defense. The maintenance of copper homeostasis requires a balance of copper uptake and export, as well as the appropriate partitioning of copper between the cytoplasm, mitochondria and secretory compartments. Although many of the proteins involved in copper homeostasis have been identified, it is unknown whether specific pathophysiological conditions lead to compensatory changes in the intracellular copper distribution. In this study, we identify changes in copper homeostasis in response to pro-inflammatory mediators. We also show a novel role for the copper-transporting ATPase, ATP7A, in the bactericidal activity of RAW264.7 macrophage cell. We also identify striking alterations in copper homeostasis in response to hypoxia in RAW264.7 macrophage cells. In response to hypoxia, we observe a change in the hierarchy of intracellular distribution favoring delivery of copper to ATP7A and to the secretory pathway, as evidenced by enhanced activity of the ferroxidase, ceruloplasmin, and by copper-dependent trafficking of ATP7A in hypoxic macrophages in vitro and in vivo. Our study underscores the potential for pathophysiological conditions to regulate adaptive responses involving altered copper distribution to cuproenzymes.eng
dc.description.bibrefIncludes bibliographical referenceseng
dc.format.extentxi, 198 pageseng
dc.identifier.oclc549097584eng
dc.identifier.urihttps://hdl.handle.net/10355/6624
dc.identifier.urihttps://doi.org/10.32469/10355/6624eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsOpenAccess.eng
dc.rights.licenseThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.
dc.subject.lcshCopper -- Metabolism -- Regulationeng
dc.subject.lcshHomeostasiseng
dc.subject.lcshAnoxemiaeng
dc.titleInflammation and hypoxia : novel regulators of mammalian copper homeostasis in macrophageseng
dc.typeThesiseng
thesis.degree.disciplineNutrition area program (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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