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Investigating the Role of FoxO1 in Regulating Protein Synthesis

Makey, Nicole Lynne

Abstract Details

2019, Doctor of Philosophy, University of Toledo, Exercise Science.
Skeletal muscle tissue is a very dynamic and adaptable organ within the human body and is regulated through a balance between protein anabolism and catabolism. It has been well established within the literature that one transcription factor, in particular, FoxO1, plays a role in the regulation of protein degradation. Conversely, there has been some evidence to suggest that FoxO1 might also play a role in the regulation of protein synthesis. Thus, our hypothesis is that the overexpression of FoxO1 influences protein synthesis through both translation efficiency (mTOR signaling), and translation capacity (ribosomal content). To determine the role that FoxO1 has on protein synthesis the gastrocnemius of transgenic mice overexpressing FoxO1 (FoxO1TG) and wild type mice were collected at 24-weeks. To determine rates of protein synthesis, mice were injected with puromycin 30 minutes prior to muscle collection. Furthermore, expression of p70sk6, a key molecule within the mTOR signaling pathway were measured via western blot. Lastly, ribosomal content was assayed by processing tissue with TRIzol and measuring total RNA on a micro-volume plate. Our findings show that FoxO1TG mice did not impact protein synthesis, ii) FoxO1TG mice did, however, cause a significant decrease in total p70s6k, iii) FoxO1TG mice also caused a significant decrease in total RNA content, iv) despite a decrease in total RNA, FoxO1TG did not impact ribosomal rRNA subunits 28S and 18S. The major finding of this study was that the overexpression of FoxO1 does not impact protein synthesis in unchallenged, resting skeletal muscle.
Thomas McLoughlin (Committee Chair)
Barry Scheuermann (Committee Member)
Abraham Lee (Committee Member)
Wendi Goodlin-Fahncke (Committee Member)
83 p.

Recommended Citations

Citations

  • Makey, N. L. (2019). Investigating the Role of FoxO1 in Regulating Protein Synthesis [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo156475521794138

    APA Style (7th edition)

  • Makey, Nicole. Investigating the Role of FoxO1 in Regulating Protein Synthesis. 2019. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo156475521794138.

    MLA Style (8th edition)

  • Makey, Nicole. "Investigating the Role of FoxO1 in Regulating Protein Synthesis." Doctoral dissertation, University of Toledo, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=toledo156475521794138

    Chicago Manual of Style (17th edition)