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toledo1270334870.pdf (324.1 KB)
ETD Abstract Container
Abstract Header
FoxO1 Induces Apoptosis in Skeletal Myotubes
Author Info
Smith, Sierra Marie
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1270334870
Abstract Details
Year and Degree
2010, Master of Science in Exercise Science, University of Toledo, College of Health Sciences.
Abstract
In treating ailments and pursuing rehabilitation, muscle atrophy is the most limiting factor effecting treatment efficiency22,34. The loss of muscle mass due to aging, inactivity, injury and disease increases the likelihood for falls, loss of independence, and decrease in quality of life8,9,20,22,23,32,34-36,39,40,44. Health care costs due to muscle atrophy run up to 18.5 billion (US) per year9. Due to the detrimental effect muscle atrophy has on both individuals and the economy; significant advances have been taken in understanding muscle atrophy and the various molecular and signaling pathways activated within the process8,9,23-25,34,35. In our previous work with the muscle atrophy process we showed that FoxO1 activation promotes muscle atrophy evidenced through the decrease in protein content, which was accompanied by signs of apoptosis, namely DNA fragmentation. To test the hypothesis that FoxO1 activation promotes expression of genes associated with muscle atrophy and apoptosis and that this reaction is dependent upon FoxO1 DNA-binding, FoxO1-estrogen receptor fusion proteins (FoxO1AAA-ER and FoxO1AAA/Arg215-ER [DNA-binding deficient]) which are activated by treatment with 4-hydroxytamoxifen (4-OHT) were stably transfected in C2C12 skeletal myoblasts using the pBABE retroviral system and grown into 4-day-old skeletal myotubes. Non-transfected C2C12 cells served as controls. After 24 hour treatment with vehicle or 4 OH-T, total RNA was isolated and gene expression performed using qPCR. The purpose of this study was to provide support for the phenotypic findings observed through assessing transcription activity of genes associated with muscle atrophy (Atrogin-1/MAFbx, Murf-1) and apoptosis (Bim, BNip3). Activation of FoxO1AAA-ER resulted in a significant increase in Atrogin-1/MAFbx (~27 fold), Bim (~3.5 fold) and Murf-1 (~2 fold) gene expression, with no significant increase in BNip3 gene expression. Whereas, activation of the FoxO1AAA/Arg215-ER resulted in a significant increase in Murf-1 (~2.2 fold), BNip3 (~2.2 fold) and Bim (~2 fold) gene expression, with no significant increase in Atrogin-1/MAFbx gene expression. No change in gene expression was observed in the control cells. These findings demonstrate that muscle atrophy induced via FoxO1 activation is associated with the induction of genes responsible for regulating protein degradation and apoptosis, via DNA binding dependent and independent mechanisms.
Committee
Thomas McLoughlin, Dr. (Advisor)
Francis Pizza, Dr. (Committee Member)
Barry Scheuermann, Dr. (Committee Member)
Pages
40 p.
Subject Headings
Biology
;
Health
Keywords
Apoptosis
;
FoxO1
;
muscle atrophy
Recommended Citations
Refworks
EndNote
RIS
Mendeley
Citations
Smith, S. M. (2010).
FoxO1 Induces Apoptosis in Skeletal Myotubes
[Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1270334870
APA Style (7th edition)
Smith, Sierra.
FoxO1 Induces Apoptosis in Skeletal Myotubes.
2010. University of Toledo, Master's thesis.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1270334870.
MLA Style (8th edition)
Smith, Sierra. "FoxO1 Induces Apoptosis in Skeletal Myotubes." Master's thesis, University of Toledo, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1270334870
Chicago Manual of Style (17th edition)
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Document number:
toledo1270334870
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Copyright Info
© 2010, all rights reserved.
This open access ETD is published by University of Toledo and OhioLINK.