Antioxidant treatment of hindlimb-unloaded mouse counteracts fiber type transition but not atrophy of disused muscles

Abstract

Oxidative stress was proposed as a trigger of muscle impairment in various muscle diseases. The hindlimb-unloaded (HU) rodent is a model of disuse inducing atrophy and slow-to-fast transition of postural muscles. Here, mice unloaded for 14 days were chronically treated with the selective antioxidant trolox. After HU, atrophy was more pronounced in the slow-twitch soleus muscle (Sol) than in the fast-twitch gastrocnemius and tibialis anterior muscles, and was absent in extensor digitorum longus muscle. In accord with the phenotype transition, HU Sol showed a reduced expression of myosin heavy chain type 2A (MHC-2A) and increase in MHC-2X and MHC-2B isoforms. In parallel, HU Sol displayed an increased sarcolemma chloride conductance related to an increased expression of ClC-1 channels, changes in excitability parameters, a positive shift of the mechanical threshold, and a decrease of the resting cytosolic calcium concentration. Moreover, the level of lipoperoxidation increased proportionally to the degree of atrophy of each muscle type. As expected, trolox treatment fully prevented oxidative stress in HU mice. Atrophy was not prevented but the drug significantly attenuated Sol phenotypic transition and excitability changes. Trolox treatment had no effect on control mice. These results suggest possible benefits of antioxidants in protecting muscle against disuse.

Depressed mitochondrial biogenesis and dynamic remodeling in mouse tibialis anterior and gastrocnemius induced by 4‐week hindlimb unloading

“…The slow twitch muscle soleus is promptly responding to unloading, while fast twitch muscles represent a less intensive response, but previous findings show that TA, GAS, and EDL can also be affected (19,20). Here, in the study, TA and GAS underwent diverse alterations following unloading.…”

“…The antigrativity soleus was considered preferentially affected and was clearly demonstrated as dysfunction of mitochondrial biogenesis following unloading (17,18). The fast-twitch muscles-EDL, GAS, and TA also respond to unloading in mouse or rat (19,20). Especially, GAS exhibited the specific dysfunction of mitochondrial respiration and TA showed distinct electromyogram following unloading (21,22).…”

Each to their own: skeletal muscles of different function use different biochemical strategies during aestivation at high temperature

“…The role of ROS and oxidative stress in disuse atrophy is further supported by work showing that mitochondria-targeting antioxidants administered to mice attenuate immobilisation atrophy (Min et al, 2011). However, results from other studies have failed to show any attenuation of disuse atrophy with antioxidant administration Desaphy et al, 2010). This disparity in results is likely due to differences in the specific antioxidants used, the ratio of the magnitude of oxidative stress (threshold level) to the magnitude of the administered antioxidant, the particular muscle tested, different conditions of disuse and combinations thereof.…”

Statin or fibrate chronic treatment modifies the proteomic profile of rat skeletal muscle

“…For instance, hindlimb unloading of rodents, a model of muscle disuse, induce a slow-to-fast transition of postural muscles, i.e. increased expression of fast isoforms of myosin heavy chain (MHC) and increase of resting gCl in soleus muscle [40]. A coordinated expression existed among MHC isoforms, metabolic enzymes and isoforms of other myofibrillar and non-myofibrillar proteins [41][42][43].…”