title: The preventive effect of β-carotene on denervation-induced soleus muscle atrophy in mice.
abstract: Muscle atrophy increases the production of reactive oxygen species and the expression of atrophy-related genes, which are involved in the ubiquitin-proteasome system. In the present study, we investigated the effects of β-carotene on oxidative stress (100 μM-H2O2)-induced muscle atrophy in murine C2C12 myotubes. β-Carotene (10 μM) restored the H2O2-induced decreased levels of myosin heavy chain and tropomyosin (P< 0·05, n 3) and decreased the H2O2-induced increased levels of ubiquitin conjugates. β-Carotene reduced the H2O2-induced increased expression levels of E3 ubiquitin ligases (Atrogin-1 and MuRF1) and deubiquitinating enzymes (USP14 and USP19) (P< 0·05, n 3) and attenuated the H2O2-induced nuclear localisation of FOXO3a. Furthermore, we determined the effects of β-carotene on denervation-induced muscle atrophy. Male ddY mice (8 weeks old, n 30) were divided into two groups and orally pre-administered micelle with or without β-carotene (0·5 mg once daily) for 2 weeks, followed by denervation in the right hindlimb. β-Carotene was further administered once daily until the end of the experiment. At day 3 after denervation, the ratio of soleus muscle mass in the denervated leg to that in the sham leg was significantly higher in β-carotene-administered mice than in control vehicle-administered ones (P< 0·05, n 5). In the denervated soleus muscle, β-carotene administration significantly decreased the expression levels of Atrogin-1, MuRF1, USP14 and USP19 (P< 0·05, n 5) and the levels of ubiquitin conjugates. These results indicate that β-carotene attenuates soleus muscle loss, perhaps by repressing the expressions of Atrogin-1, MuRF1, USP14 and USP19, at the early stage of soleus muscle atrophy.
authors.affiliation: Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ogawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kariya
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kitakaze
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Yamaji
authors.forename: Naoki
authors.initials: N
authors.lastname: Harada
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hosotani
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nakano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inui
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide; D008297:Male; D051379:Mice; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000294:innervation* / Q000378:metabolism; D009133:Muscular Atrophy / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000201:enzymology; D018384:Oxidative Stress / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*; D019207:beta Carotene / Q000494:pharmacology*
chemical_list: D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D009124:Muscle Proteins; D017392:Thiobarbituric Acid Reactive Substances; C469268:Usp14 protein, mouse; D019207:beta Carotene; D006861:Hydrogen Peroxide; D043743:Ubiquitin-Protein Ligase Complexes; D043222:Ubiquitin Thiolesterase