PRMT biology during skeletal muscle disuse. / Protein arginine methyltransferase 1 (PRMT1), PRMT4 (also known as
co-activator-associated arginine methyltransferase 1; CARM1), and PRMT5 are
critical components of a diverse set of intracellular functions. Despite the limited
number of studies in skeletal muscle, evidence strongly suggests that these
enzymes are important players in the regulation of phenotypic plasticity. However,
their role in disuse-induced muscle remodelling is unknown. Thus, we sought to
determine whether denervation-induced muscle disuse alters PRMT expression
and activity in skeletal muscle within the context of early signaling events that
precede muscle atrophy. Mice were subjected to 6, 12, 24, 72, or 168 hours of
unilateral hindlimb denervation. The contralateral limb served as an internal
control. Muscle mass decreased by ~30% following 168 hours of disuse. Prior to
atrophy, the expression of muscle RING finger 1 and muscle atrophy F-box were
significantly elevated. The expression and activities of PRMT1, CARM1, and
PRMT5 displayed differential responses to muscle disuse. Peroxisome
proliferator-activated receptor-γ coactivator-1α, AMP-activated protein kinase
(AMPK), and p38 mitogen-activated protein kinase expression and activation
were altered as early as 6 hours after denervation, suggesting that adaptations in
these molecules are among the earliest signals that precede atrophy. AMPK
activation also predicted changes in PRMT expression and function following
disuse. Our study indicates that PRMTs are important for the mechanisms that
precede, and initiate muscle remodelling in response to neurogenic disuse. / Thesis / Master of Science (MSc) / Skeletal muscle is a plastic tissue that is capable of adapting to various
physiological demands. Previous work suggests that protein arginine
methyltransferases (PRMTs) are important players in the regulation of skeletal
muscle remodelling. However, their role in disuse-induced muscle plasticity is
unknown. Therefore, the purpose of this study was to investigate the role of
PRMTs within the context of early, upstream signaling pathways that mediate
disuse-evoked muscle remodelling. We found differential responses of the
PRMTs to muscle denervation, suggesting a unique sensitivity to, or regulation by,
potential upstream signaling pathways. AMP-activated protein kinase (AMPK)
was among the molecules that experienced a rapid change in activity following
disuse. These alterations in AMPK predicted many of the modifications in PRMT
biology during inactivity, suggesting that PRMTs factor into the molecular
mechanisms that precede neurogenic muscle atrophy. This study expands our
understanding of the role of PRMTs in regulating skeletal muscle plasticity.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/20740 |
| Date | January 2017 |
| Creators | Stouth, Derek W. |
| Contributors | Ljubicic, Vladimir, Kinesiology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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