Shared more. Cited more. Safe forever.
    • advanced search
    • submit works
    • about
    • help
    • contact us
    • login
    View Item 
    •   MOspace Home
    • University of Missouri-Columbia
    • Graduate School - MU Theses and Dissertations (MU)
    • Theses and Dissertations (MU)
    • Dissertations (MU)
    • 2009 Dissertations (MU)
    • 2009 MU dissertations - Access restricted to MU
    • View Item
    •   MOspace Home
    • University of Missouri-Columbia
    • Graduate School - MU Theses and Dissertations (MU)
    • Theses and Dissertations (MU)
    • Dissertations (MU)
    • 2009 Dissertations (MU)
    • 2009 MU dissertations - Access restricted to MU
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    advanced searchsubmit worksabouthelpcontact us

    Browse

    All of MOspaceCommunities & CollectionsDate IssuedAuthor/ContributorTitleIdentifierThesis DepartmentThesis AdvisorThesis SemesterThis CollectionDate IssuedAuthor/ContributorTitleIdentifierThesis DepartmentThesis AdvisorThesis Semester

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular AuthorsStatistics by Referrer

    Regulation of copper homeostasis and inflammation in microglial cells

    Zheng, Zhiqiang, 1977-
    View/Open
    [PDF] public.pdf (2.156Kb)
    [PDF] short.pdf (20.52Kb)
    [PDF] research.pdf (3.478Mb)
    Date
    2009
    Format
    Thesis
    Metadata
    [+] Show full item record
    Abstract
    [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Disturbed copper homeostasis has been shown to implicate in the pathogenesis of AD, as evidenced by high accumulation of copper in the senile plaques. In this study, it was demonstrated that the expression of the copper exporter ATP7A was specifically up-regulated in activated microglial cells in the transgenic AD mouse model TgCRND8. The expression of ATP7A was also increased by the pro-inflammatory cytokine IFN-[gamma] in the mouse microglial cell line in vitro. Besides, IFN-[gamma] also induced the relocation of ATP7A from Golgi to cytoplasmic vesicles and increased copper uptake, resulting in its accumulation. All these evidence strongly supports a model that inflammation in AD promotes the uptake of copper in microlgial cells, which are activated and surround the senile plaques. This may offer protection by sequestering the interaction of copper with amyloid peptides, which has been shown toxic to neuronal cells. As the major source of nitric oxide, iNOS expression is induced by inflammatory conditions. In this study, it was shown that iNOS expression induced by LPS was suppressed by physiological levels of copper at transcriptional level. The induction of iNOS was also suppressed in the ATP7A knockdown microglial cells, suggesting the importance of copper homeostasis in the regulation of iNOS expression. As the major transcriptional factor responsible for iNOS regulation, NF-[kappa]B activation was inhibited by copper treatment. Collectively, this study reveals the novel role of copper in the regulation of NF-[kappa]B and its target genes.
    URI
    https://hdl.handle.net/10355/6885
    https://doi.org/10.32469/10355/6885
    Degree
    Ph. D.
    Thesis Department
    Nutrition area program (MU)
    Rights
    Access is limited to the campus of the University of Missouri--Columbia.
    This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.
    Collections
    • 2009 MU dissertations - Access restricted to MU
    • Nutrition and Exercise Physiology electronic theses and dissertations (MU)

    Send Feedback
    hosted by University of Missouri Library Systems
     

     


    Send Feedback
    hosted by University of Missouri Library Systems