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Asim Shaikh Ken Yu Nabil Haider

Abstract

Introduction: Protein arginine methyltransferases (PRMTs) are an important class of enzymes that catalyze post-translational modification of arginine residues on histone or nonhistone substrates. In skeletal muscle, PRMT1 expression has been linked to muscle homeostasis, regeneration, metabolism, and synthesis. The expression of PRMT1 in skeletal muscle has already been shown to be induced by treadmill exercise, however, the relationship between PRMT1 and skeletal muscle hypertrophy remains unexplored. This study aims to determine the significance of PRMT1 in muscle hypertrophy by identifying whether wild-type mice (WT) experience elevated levels of exercise-induced muscle hypertrophy compared to PRMT1-knockout mice (KO).


Methods: 6 month old mice will be split into male (M) and female (F) groups. Both M and F groups will then be randomly distributed to WT and KO groups. WT M, KO M, WT F, and KO F groups will be further randomly divided into sedentary (SED) and exercise (EX) groups. EX groups will undergo a resistance training program for 8 weeks while SED groups will be at rest. All mice will be euthanized by cervical dislocation while at rest by the end of the 8 weeks and their tissue samples will be collected. The progression of muscle hypertrophy between groups will be assessed weekly using Bioseb grip strength tests in grams normalized to body mass in grams (g/g). Following the 3 months, muscle biopsies of the tibialis anterior (TA) muscle will be taken to perform fluorescence staining of the myofibers. Primary and secondary antibodies against myosin heavy chain I, IIa, IIx, and IIb will be used to stain cross-sectional areas. The quantity and cross-sectional area of the fast-glycolytic fibers will be measured to quantify muscle hypertrophy between WT and KO groups.


Anticipated Results: The Bioseb grip strength tests and TA immunostaining should demonstrate that WT mice have greater grip strength and a higher quantity of myofibers with larger cross-sectional areas compared to KO mice.


Conclusion: These results would demonstrate the importance of PRMT1 in facilitating exercise-induced muscle hypertrophy. Future directions may involve exploring downstream signaling molecules of PRMT1 to identify potential PRMT1 upregulators, accelerating muscle hypertrophy and combating pathological muscle atrophy.

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Section
Research Protocol