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Does Proteasome Activity Impact Skeletal Muscle Hypertrophy?

Abstract Details

2019, Doctor of Philosophy, University of Toledo, Exercise Science.
The Ubiquitin-Proteasome System (UPS) is the primary machinery responsible for protein degradation within skeletal muscle. There is evidence to suggest that the proteasome is activated during skeletal muscle hypertrophy, indicating a causative relationship between hypertrophy and protein degradation. However, there is no evidence to suggest the direct role that the proteasome plays on skeletal muscle growth. Therefore, the purpose of this study was to pharmacologically inhibit the proteasome in order to directly measure its contribution to skeletal muscle hypertrophy. Given the relationship between proteasome activity and hypertrophy, we hypothesized that upon inhibition of the proteasome there would be a reduction in skeletal muscle hypertrophy. To determine the role of the proteasome on skeletal muscle hypertrophy, a 10-day bilateral synergist ablation or a sham surgery was utilized. Twice daily injections of 7.5mg/kg MG-132 or vehicle (20g/L carboxymethylcellulose + 2.5g/L Tween-20 + 20% DMSO) were administered during this time. To determine the extent of muscle hypertrophy, plantaris muscles were weighed directly after excision, and whole muscle and individual fiber CSA were analyzed. Release of fluorescent signal was monitored over a two-hour time point. Additionally, total ubiquitination was measured through western blotting. Our findings show that i) proteasome activity is increased following synergist ablation ii) inhibition of the proteasome resulted in a reduced response in hypertrophy following synergist ablation iii) total ubiquitination increased following synergist ablation but was attenuated following MG-132 administration. The major finding of this study was that proteasome activity increased following chronic overload, and when the proteasome was inhibited, hypertrophy did not occur to the same extent. Therefore, our findings suggest that an increase in proteasome activity is necessary to support exercise-induced skeletal muscle hypertrophy.
Thomas McLoughlin (Advisor)
Barry Scheuermann (Committee Member)
Abraham Lee (Committee Member)
Wendi Goodlin-Fahncke (Committee Member)
75 p.

Recommended Citations

Citations

  • Lozar, O. M. (2019). Does Proteasome Activity Impact Skeletal Muscle Hypertrophy? [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1576264202406223

    APA Style (7th edition)

  • Lozar, Olivia. Does Proteasome Activity Impact Skeletal Muscle Hypertrophy? 2019. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1576264202406223.

    MLA Style (8th edition)

  • Lozar, Olivia. "Does Proteasome Activity Impact Skeletal Muscle Hypertrophy?" Doctoral dissertation, University of Toledo, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1576264202406223

    Chicago Manual of Style (17th edition)