Abstract
Severe muscle weakness concomitant with preferential depletion of myosin has been observed in several pathological conditions. Here, we used the steroid-denervation (S-D) rat model, which shows dramatic decrease in myosin content and force production, to test whether electrical stimulation (ES) treatment can prevent these deleterious changes. S-D was induced by cutting the sciatic nerve and subsequent daily injection of dexamethasone for 7 days. For ES treatment, plantarflexor muscles were electrically stimulated to produce four sets of five isometric contractions each day. Plantarflexor in situ isometric torque, muscle weight, skinned muscle fiber force, and protein and mRNA expression were measured after the intervention period. ES treatment partly prevented the S-D-induced decreases in plantarflexor in situ isometric torque and muscle weight. ES treatment fully prevented S-D-induced decreases in skinned fiber force and ratio of myosin heavy chain (MyHC) to actin, as well as increases in the reactive oxygen/nitrogen species-generating enzymes NADPH oxidase (NOX) 2 and 4, phosphorylation of p38 MAPK, mRNA expression of the muscle-specific ubiquitin ligases muscle ring finger-1 (MuRF-1) and atrogin-1, and autolyzed active calpain-1. Thus, ES treatment is an effective way to prevent muscle impairments associated with loss of myosin.
Highlights
Decreased muscle mass is an obvious cause of muscle weakness, but it is becoming increasingly clear that impairments intrinsic to the muscle fibers often make an important contribution to the loss of muscles strength (Reid and Moylan, 2011)
electrical stimulation (ES) treatment had no effect in control rats, whereas in S-D rats it attenuated the decrease in muscle weight for the fast-twitch plantaris and gastrocnemius muscles, but not for the slow-twitch soleus muscles
The S-D induced a severe depression in in situ plantarflexor torque (Figures 2A,B). This torque depression was still present after normalizing to the whole muscle weight (Figure 2C), which implies that it was due to the combined effect of decreased muscle cross-sectional area and defective activation and/or contractile function of the muscle fibers
Summary
Decreased muscle mass is an obvious cause of muscle weakness, but it is becoming increasingly clear that impairments intrinsic to the muscle fibers often make an important contribution to the loss of muscles strength (Reid and Moylan, 2011). The exact mechanisms underlying the myosin loss are not Electrical Stimulation Prevents Myosin Loss clear, but reduced mechanical stress and increased glucocorticoid signaling are considered to have important roles (Rouleau et al, 1987; Larsson et al, 2000; Borina et al, 2010; Brocca et al, 2015; Minetto et al, 2015). Increased ROS/RNS production was observed in skeletal muscle from rats with glucocorticoid-induced myopathy (Konno, 2005). Signaling via the p38 mitogen-activated protein kinase (MAPK) pathway has been proposed to mediate oxidative stress-induced atrogin-1 expression and ubiquitin-conjugating activity in skeletal muscle (Li et al, 2005; Jin and Li, 2007)
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