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DC Field | Value | Language |
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dc.contributor.advisor | Ljubicic, Vladimir | - |
dc.contributor.author | Webb, Erin Kristena | - |
dc.date.accessioned | 2023-01-26T15:43:58Z | - |
dc.date.available | 2023-01-26T15:43:58Z | - |
dc.date.issued | 2022 | - |
dc.identifier.uri | http://hdl.handle.net/11375/28249 | - |
dc.description.abstract | Coactivator-associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of arginine residues on target proteins critical for health and disease. The purpose of this study was to characterize the effects of short-term, pharmacological CARM1 inhibition on skeletal muscle size, function, and atrophy. Adult mice (n = 10-11/sex) were treated with either a CARM1 inhibitor (150 mg/kg EZM2302; EZM) or vehicle (Veh) via oral gavage for 11-13 days and muscle mass, function, and exercise capacity were assessed. Additionally, we investigated the effect of CARM1 suppression on unilateral hindlimb denervation (DEN)-induced muscle atrophy (n = 8/sex). We report that CARM1 inhibition caused significant reductions in the asymmetric dimethylation of known CARM1 substrates but no change in CARM1 protein or mRNA content in skeletal muscle. Reduced CARM1 activity did not affect body or muscle mass, however, we observed a decrease in exercise capacity and muscular endurance in male mice. CARM1 methyltransferase activity increased in the muscle of Veh-treated mice following 7 days of DEN and this response was blunted in EZM-dosed mice. Skeletal muscle mass and myofiber cross-sectional area were significantly reduced in DEN compared to contralateral, non-DEN limbs to a similar degree in both treatment groups. Furthermore, skeletal muscle atrophy and autophagy gene expression programs were elevated in response to DEN independent of CARM1 suppression. Collectively, these results suggest that short-term, pharmacological CARM1 inhibition in adult animals affects muscle performance in a sex-specific manner but does not impact the maintenance and remodeling of skeletal muscle mass during conditions of neurogenic muscle atrophy. | en_US |
dc.language.iso | en | en_US |
dc.title | EFFECTS OF SHORT-TERM, PHARMACOLOGICAL CARM1 INHIBITION ON SKELETAL MUSCLE MASS, FUNCTION, AND ATROPHY | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Kinesiology | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science in Kinesiology | en_US |
dc.description.layabstract | Coactivator-associated arginine methyltransferase 1 (CARM1) is an enzyme that alters the activity of other proteins. CARM1 plays an important role in several tissues, however, little is understood about its function in skeletal muscle. Recent research suggests that CARM1 could be involved in the process of skeletal muscle wasting and weakness, termed muscle atrophy. Therefore, we aimed to study the effects of short-term pharmacological CARM1 inhibition on skeletal muscle mass, function, and atrophy in adult mice. Our observations show that treatment with a CARM1-inhibiting compound was very effective at reducing CARM1 activity in muscle. CARM1 inhibition did not affect muscle mass, but it did decrease muscular endurance, particularly in male mice. Suppressed CARM1 activity had no impact on muscle wasting or molecular atrophy signalling following a period of denervation-evoked muscle disuse. Collectively, we demonstrate that short-term CARM1 inhibition impacts muscle performance without affecting the maintenance and plasticity of muscle mass. | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
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File | Description | Size | Format | |
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Webb_Erin_K_December2022_MSc.pdf | 20.41 MB | Adobe PDF | View/Open |
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