Novel roles of FKBP5 in muscle alteration induced by gravity change in mice.
Skeletal muscle hypertrophy and wasting are induced by hypergravity and microgravity, respectively. However, the mechanisms by which gravity change regulates muscle mass still remain unclear. We previously reported that hypergravity increases muscle mass via the vestibular system in mice. In this study, we performed comparative DNA microarray analysis of the soleus muscle from mice kept in 1 or 3 g environments with or without vestibular lesions. Mice were kept in 1 g or 3 g environment for 4 weeks by using a centrifuge 14 days after surgical bilateral vestibular lesions. FKBP5 was extracted as a gene whose expression was enhanced by hypergravity through the vestibular system. Stable FKBP5 overexpression increased the phosphorylations of Akt and p70 S6 kinase (muscle protein synthesis pathway) and myosin heavy chain, a myotube gene, mRNA level in mouse myoblastic C2C12 cells, although it reduced the mRNA levels of atrogin-1 and MuRF1, muscle protein degradation-related genes. In conclusion, we first showed that FKBP5 is induced by hypergravity through the vestibular system in anti-gravity muscle of mice. Our data suggest that FKBP5 might increase muscle mass through the enhancements of muscle protein synthesis and myotube differentiation as well as an inhibition of muscle protein degradation in mice.
Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan.
Takeshi
T
Shimoide
Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan.
Naoyuki
N
Kawao
Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan.
Yukinori
Y
Tamura
Department of Physiology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Hironobu
H
Morita
Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan. Electronic address: hkaji@med.kindai.ac.jp.
Hiroshi
H
Kaji
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation; D006112:Gravitation; D018471:Hypergravity; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000070584:Tripartite Motif Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5
D009124:Muscle Proteins; D012333:RNA, Messenger; D044843:SKP Cullin F-Box Protein Ligases; D022021:Tacrolimus Binding Proteins; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D000099159:Tacrolimus Binding Protein 5; C486691:Fbxo32 protein, mouse; C499084:Trim63 protein, mouse
FKBP5; Gravity; Muscle; Myoblast; Vestibular system