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    Deciphering the Role of FXR1 in Cardiac Hypertrophy

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    azu_etd_hr_2017_0165_sip1_m.pdf
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    Author
    Patel, Parth Mahendra
    Issue Date
    2017
    Advisor
    Gregorio, Carol
    
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    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
    Rationale: Cardiac hypertrophy is the enlargement of the heart and can be induced by pathological and non-pathological events. The Fragile X family of RNA-binding proteins have been shown to be involved in cardiac structure and development (Mientjes et al, 2004) (Padje et al, 2009). Potential links between FXR1 and hypertrophy have not been significantly studied. Objective: To study the effect that varying expression of FXR1 has upon hypertrophy, and the molecular role FXR1 plays in hypertrophy. Method and Results: Following a voluntary running protocol, FXR1 wild-type mice had significant cardiac hypertrophy while FXR1 heterozygous mice (reduced FXR1 expression) had a blunted response with no significant hypertrophy. Cardiomyocyte size analysis showed that FXR1 overexpression (~9-fold increase) caused significant size reduction and FXR1 knockdown caused significant size increase. RNA immunoprecipitation showed multiple components of the PI3K/AKT/mTOR pathway associating with FXR1 in a protein/RNA complex. Western blotting showed that exercised FXR1 heterozygous mice had an increased expression of phosphorylated AKT versus non-exercised wild-type mice. Varying FXR1 expression in cells did not affect p-AKT expression. Conclusions: The amount of FXR1 in mice and cells appears to alter the severity of cardiac hypertrophy. FXR1 may regulate cardiac hypertrophy, but how this occurs is still unclear.
    Type
    text
    Electronic Thesis
    Degree Name
    B.S.
    Degree Level
    bachelors
    Degree Program
    Honors College
    Molecular and Cellular Biology
    Degree Grantor
    University of Arizona
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    Honors Theses
    Honors Theses

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