• Login
    View Item 
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UA Campus RepositoryCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournal

    My Account

    LoginRegister

    About

    AboutUA Faculty PublicationsUA DissertationsUA Master's ThesesUA Honors ThesesUA PressUA YearbooksUA CatalogsUA Libraries

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Cellular and biochemical consequences of ornithine decarboxylase regulation

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    azu_td_9706691_sip1_m.pdf
    Size:
    3.322Mb
    Format:
    PDF
    Download
    Author
    Tome, Margaret Ellen
    Issue Date
    1996
    Keywords
    Biology, Cell.
    Chemistry, Biochemistry.
    Advisor
    Gerner, Eugene W.
    
    Metadata
    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    The polyamines are abundant polycations necessary for eucaryotic cell growth. Ornithine decarboxylase (ODC), the first and often rate-limiting enzyme in polyamine biosynthesis, is responsible for the formation of putrescine, the precursor for polyamine synthesis. ODC is normally very tightly regulated by a complex interaction of control of both synthesis and degradation. Regulation of ODC synthesis allows cells to increase ODC in response to various stimuli; however, the importance of the rapid degradation of ODC in cellular metabolism is less well understood. The studies presented here have compared the parental, HTC cells, which exhibit rapid ODC degradation, to two cell lines, DH23A and HMOA, which express a more stable ODC, to examine the cellular consequences of aberrant ODC expression. Aberrantly elevated ODC in DH23A cells results in a dramatic accumulation of endogenous putrescine, a decrease in cell number and the appearance of apoptotic cells. In contrast, HTC cells, with moderate polyamine contents, can be maintained in exponential growth. Accumulation of similar concentrations of putrescine from an exogenous source mimics the effect of ODC overexpression. This suggests that putrescine is the causative agent or trigger of apoptosis. Accumulation of excess intracellular putrescine inhibits the formation of modified eIF-5A in vivo. eIF-5A is a protein that is post-translationally modified by spermidine. Although the function is unclear, both eIF-5A and the modification by spermidine are necessary for growth in eucaryotic cells. Treatment of DH23A cells with diaminoheptane(DAH), an in vitro inhibitor of eIF-5A modification, both inhibits the modification of eIF-5A in vivo and increases apoptosis. DAH appears to cause a decrease in cell number by acting as a competitive inhibitor of the post-translational modification of eIF-5A by spermidine. Putrescine probably inhibits the formation of modified eIF-5A upstream of the spermidine addition, but not at the level of transcription. These data support the hypothesis that the rapid degradation of ODC may be a protective mechanism to avoid cell toxicity due to putrescine accumulation and suggest that suppression modified eIF-5A formation is one mechanism by which cells may be induced to undergo apoptosis.
    Type
    text
    Dissertation-Reproduction (electronic)
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Graduate College
    Biochemistry
    Degree Grantor
    University of Arizona
    Collections
    Dissertations

    entitlement

     
    The University of Arizona Libraries | 1510 E. University Blvd. | Tucson, AZ 85721-0055
    Tel 520-621-6442 | repository@u.library.arizona.edu
    DSpace software copyright © 2002-2017  DuraSpace
    Quick Guide | Contact Us | Send Feedback
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.