Glucocorticoid-induced alterations in titin, nebulin, myosin heavy chain isoform content and viscoelastic properties of rat skeletal muscle

Abstract

Viscoelastic properties of skeletal muscle are associated with a complex network of cytoskeletal proteins where titin and nebulin play a substantial role. The need for evaluation of muscle viscoelastic properties is widely accepted in clinical use to evaluate the effect of treatment or progression of muscle pathology (atrophy). We tested the hypothesis that the viscoelastic properties (elasticity, tone and stiffness) change in atrophied muscles with concomitant changes in cytoskeletal proteins (titin, nebulin) and contractile protein (myosin heavy chain) proportion. Sixteen 24-week-old male rats of the Wistar strain were randomly allocated to two groups: dexamethasone group treated each day for 10 consecutive days with dexamethasone in order to induce atrophy and control group. Skeletal muscle viscoelastic properties (elasticity, tone and stiffness) were determined using a myotonometer. Titin, nebulin and myosin heavy chain content were quantified using SDS-PAGE electrophoresis. We found that glucocorticoid-induced muscle atrophy is accompanied by reduced elasticity and increased tone and stiffness, with concomitant changes in titin, nebulin and myosin heavy chain content. The elasticity decreased by 10.9% (P < 0.05), tone increased from 26.69 Hz to 37.73 Hz (P < 0.05), and stiffness was significantly lower in dexamethasone group (627.3 N/m vs 758.6 N/m); (P < 0.05). Compared with the control group, the content of titin, nebulin and myosin heavy chain in atrophied muscle was 76.4%, 70.6% and 82.3%, respectively. Our results may lead to a better understanding of the mechanism of muscle atrophy and provide better guidance for rehabilitation practices and help to find rational therapeutic intervention in the future.

Role of Myofibrillar Protein Catabolism in Development of Glucocorticoid Myopathy: Aging and Functional Activity Aspects

“…It has been shown that glucocorticoid myopathic FT muscles’ neuromuscular synapses are destroyed [ 2 ]. A decrease of titin and myosin [ 21 ] and of the ratio of nebulin and MyHC in myopathic muscle [ 12 ], shows that these changes in contractile and elastic proteins are the result of elevated catabolism of the abovementioned proteins in skeletal muscle. This is the reason for reduced elasticity and generation of tension in glucocorticoid-caused myopathic muscle.…”

“…Viscoelastic properties illustrate skeletal muscle function in physiopathological conditions. There is a positive correlation between muscle atrophy and elasticity and a negative correlation between state of atrophy and muscle tone [ 12 ]. A decrease in contractile protein myosin and in elastic proteins titin and nebulin leads to the reduction of muscle elasticity and generation of tension in myopathic muscle [ 12 ].…”

“…There is a positive correlation between muscle atrophy and elasticity and a negative correlation between state of atrophy and muscle tone [ 12 ]. A decrease in contractile protein myosin and in elastic proteins titin and nebulin leads to the reduction of muscle elasticity and generation of tension in myopathic muscle [ 12 ]. A decrease in the oxidative capacity and contractile properties in elderly and myopathic muscle are the reasons for changes in muscle quantity and quality, which lead to disability.…”

“…So, myofibrils of glucocorticoids caused myopathic IIB muscle fibers (fibers with low oxidative capacity) to show disarray of myosin myofilaments, increased proteolytic activity [ 10 ], a decreased synthesis rate of myosin and actin [ 9 ], and a decrease in myosin-heavy chain (MyHC) IIb isoforms’ relative content [ 11 ]. Reduced muscle elasticity, increased tone, and stiffness with a concomitant decrease in cytoskeletal proteins titin and nebulin and contractile protein myosin content are accompanied by muscle atrophy [ 12 ]. Both glucocorticoids caused myopathic and aging-caused sarcopenic muscle wasting is mainly a result of decrease of FT muscle fibers and atrophy of these fibers [ 13 ].…”