Transcriptional Regulation of Forkhead Box O3 (FoxO3) and Manganese Superoxide Dismutase (MnSOD)

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Material Information

Title:
Transcriptional Regulation of Forkhead Box O3 (FoxO3) and Manganese Superoxide Dismutase (MnSOD) In Vivo Applications
Physical Description:
1 online resource (181 p.)
Language:
english
Creator:
Barilovits, Sarah J
Publisher:
University of Florida
Place of Publication:
Gainesville, Fla.
Publication Date:

Thesis/Dissertation Information

Degree:
Doctorate ( Ph.D.)
Degree Grantor:
University of Florida
Degree Disciplines:
Medical Sciences, Biochemistry and Molecular Biology (IDP)
Committee Chair:
NICK,HARRY S
Committee Co-Chair:
BLOOM,LINDA B
Committee Members:
BUNGERT,JORG
KILBERG,MICHAEL S
WATERS,MICHAEL F

Subjects

Subjects / Keywords:
foxo3 -- mnsod -- nutrient -- transcription
Biochemistry and Molecular Biology (IDP) -- Dissertations, Academic -- UF
Genre:
Medical Sciences thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract:
Cells have a variety of defenses for responding to stress.In the case of oxidative stress, the antioxidant enzyme manganese superoxide dismutase (MnSOD) is a key player in detoxifying reactive oxygen species (ROS). Our laboratory has previously demonstrated that MnSOD is regulated by the transcription factors Foxo3 and C/EBPß. Foxo3 specifically regulates MnSOD in response to nutrient stress. This observation led to the hypothesis that Foxo3itself may be regulated by nutrient stress. Our data indicate that Foxo3 is transcriptionally induced in response to essential amino acid deprivation inhuman HepG2 cells, and that the transcription factors ATF4 and c-Myc are involved in this upregulation. Foxo3 mRNA is also stabilized in response to nutrient stress. Foxo3 has been shown to be a critical factor in ovarian folliculogenesis, and we hypothesized that we could use the nutrient-dependent regulation of Foxo3 to affect follicular development in vivo. Treatment of mice with a glucose deprivation mimetic, 2-deoxyglucose(2-DG), led to an increase in Foxo3 mRNA expression in the ovary and resulted in a block to follicular activation. These data demonstrate that Foxo3regulation by nutrient deprivation plays a key role in fertility. Overexpression or induction of MnSOD has been demonstrated to be cytoprotective against a variety of stresses. Our laboratory has shown that C/EBPß, specifically its LAP* form,is required for IL-1ß-dependent induction of MnSOD. Interestingly, overexpression of LAP* in cell culture is sufficient to induce endogenous MnSOD. We hypothesized that cellular delivery of C/EBPß could upregulate MnSOD and provide a cytoprotective effect. Our studies show that LAP* fused to a cell-penetrating peptide (CPP) can be expressed and purified from mammalian cells, and indicate that this method may be useful for the upregulation of MnSOD prior to cellular stress.
General Note:
In the series University of Florida Digital Collections.
General Note:
Includes vita.
Bibliography:
Includes bibliographical references.
Source of Description:
Description based on online resource; title from PDF title page.
Source of Description:
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility:
by Sarah J Barilovits.
Thesis:
Thesis (Ph.D.)--University of Florida, 2013.
Local:
Adviser: NICK,HARRY S.
Local:
Co-adviser: BLOOM,LINDA B.
Electronic Access:
RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2014-12-31

Record Information

Source Institution:
UFRGP
Rights Management:
Applicable rights reserved.
Classification:
lcc - LD1780 2013
System ID:
UFE0046102:00001