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

    Browse

    All of TUScholarShareCommunitiesDateAuthorsTitlesSubjectsGenresThis CollectionDateAuthorsTitlesSubjectsGenres

    My Account

    LoginRegister

    Help

    AboutPeoplePoliciesHelp for DepositorsData DepositFAQs

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    MECHANISMS OF G PROTEIN-COUPLED RECEPTOR 2 REGULATION AND INHIBITION IN CARDIOVASCULAR DISEASE AND AGING

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Lieu_temple_0225E_14152.pdf
    Size:
    6.775Mb
    Format:
    PDF
    Download
    Genre
    Thesis/Dissertation
    Date
    2020
    Author
    Lieu, Melissa
    Advisor
    Koch, Walter J
    Committee member
    Houser, Steven R.
    Kishore, Raj
    Drosatos, Konstantinos
    Sato, Priscila
    Department
    Biomedical Sciences
    Subject
    Molecular Biology
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/285
    
    Metadata
    Show full item record
    DOI
    http://dx.doi.org/10.34944/dspace/269
    Abstract
    G protein-coupled receptor kinase 2 (GRK2) has been a thriving therapeutic target for cardiovascular disease treatment since its discovery for desensitizing and downregulating b-adrenergic receptors that are vital to cardiac function. GRK2 inhibition through a variety of methods in animal models of cardiac ischemia and heart failure achieved improvements in cardiac function, hemodynamic function, cardiomyocyte apoptosis, and fibrotic scar size among many other observations. Although GRK2 has been used as a therapeutic tool in multiple studies, its mechanisms of regulation are necessary to understand its role in disease pathogenesis and therapeutic application. This dissertation comprises two projects (1) investigating the microRNA (miRNA) regulation of GRK2 and (2) investigating the impact of loss of dynamic regulation of GRK2 through S-nitrosylation. (1) Candidate miRNAs were selected from miRNA microarray analysis of miRNA differential expression data and bioinformatic prediction. In vitro validation of kshv-miR- K12-3-5p and hsa-miR-181a-5p have shown their ability to bind to the GRK2 3’UTR as well as significantly decrease GRK2 mRNA or protein. The successful regulation of GRK2 through these miRNAs warrant in vivo application and investigation as GRK2-targeting HF therapy in a mouse model of HF. (2) In order to determine the impact of chronic GRK2 overactivity, mice that contained a knock-in mutation of GRK2 Cys340àSer (GRK2- C340S), a site of dynamic inhibitory regulation by S-nitrosylation, were allowed to age >12 months. Loss of S-nitrosylation of GRK2 was sufficient to cause cardiovascular remodeling and dysfunction over time.
    ADA compliance
    For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
    Collections
    Theses and Dissertations

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Temple University Libraries | 1900 N. 13th Street | Philadelphia, PA 19122
    (215) 204-8212 | scholarshare@temple.edu
    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.