Prevention of unloading-induced atrophy by vitamin E supplementation: links between oxidative stress and soleus muscle proteolysis?
Exposure to reduced activity induces skeletal muscle atrophy. Oxidative stress might contribute to muscle wasting via proteolysis activation. This study aimed to test two hypotheses in rats. First, supplementation of the antioxidant vitamin E, prior and during the phase of unloading, would partly counteract unloading-induced soleus muscle atrophy. Secondly, vitamin E supplementation would decrease the rate of muscle proteolysis by reducing expression of calpains, caspases-3, -9, and -12, and E3 ubiquitin ligases (MuRF1 and MAFbx). Soleus muscle atrophy (-49%) induced by 14 days of hindlimb unloading was reduced to only 32% under vitamin E. Vitamin E partly prevented the decrease in type I and IIa fiber size. Supplementation increased HSP72 content and suppressed the rise in muscle level of thiobarbituric acid-reactive substance caused by unloading but failed to modify the lower ratio of reduced vs oxidized glutathione, the higher uncoupling proteins mRNA, and the antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) observed after unloading. Vitamin E treatment abolished the large upregulation of caspases-9 and -12 and MuRF1 transcripts in unloaded muscle and greatly decreased the upregulation of mu-calpain, caspase-3, and MAFbx mRNA. In conclusion, the protective effect of vitamin E might be due to modulation of muscle proteolysis-related genes rather than to its antioxidant function.
Servais
Stéphane
S
Laboratoire de Physiologie Intégrative, Cellulaire et Moléculaire, UMR 5123 CNRS, Université Claude Bernard Lyon 1, Bât Raphael Dubois 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex 09, France.
Letexier
Dominique
D
Favier
Roland
R
Duchamp
Claude
C
Desplanches
Dominique
D
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D019587:Dietary Supplements; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D019417:Hindlimb Suspension; D015227:Lipid Peroxidation; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology*; D009133:Muscular Atrophy / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; D014810:Vitamin E; D005978:Glutathione