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mTOR Pathway Activation Following Sciatic Stimulation in Wild-Type and Desmin Knockout Mice

The 52 kDa intermediate filament protein desmin plays an important role in force transmission in skeletal muscle by connecting myofibrils at Z-lines and to the sarcolemma. Desmin content in muscle adapts to contractile activity and may be involved in cellular signaling mechanisms responsible for muscle growth. Purpose: To compare signaling responses of the mTOR pathway in wild type (WT) vs desmin knock out (KO) mice. Methods: WT (n=12) and KO (n=12) mice were exposed to high frequency electric stimulation of the left hindlimb to elicit an acute response of the mTOR pathway. Non-stimulated right hindlimbs were used as a within animal control. Right and left TA and EDL muscles were dissected 30 min post-stimulation and examined for changes in mTOR, 4E-BP1 and p70S6K. Results: Relative to WT control samples, total mTOR and total 4E-BP1 content was higher in KO control samples. Electrical stimulation resulted in an increase p70S6K phosphorylation in WT and KO animals however there was no difference between the groups. 4E-BP1 phosphorylation was increased in WT but not KO following electrical stimulation. There was no change in mTOR phosphorylation in response to stimulation in WT or KO. Conclusion: The absence of desmin in skeletal muscle does not impair the phosphorylation of p70S6K demonstrating that a tensile load on the muscle will likely result in an increase in protein synthesis. Elevated levels of total mTOR and 4E-BP1 may imply an adaptation to increase sensitivity to growth stimuli in the muscle.

Identiferoai:union.ndltd.org:BGMYU2/oai:scholarsarchive.byu.edu:etd-4502
Date13 December 2012
CreatorsNelson, Daniel S.
PublisherBYU ScholarsArchive
Source SetsBrigham Young University
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceTheses and Dissertations
Rightshttp://lib.byu.edu/about/copyright/

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