Submitted on May 30, 2006
Accepted on December 15, 2006
Role(s) of nucleoli, phosphorylation of ribosomal protein S6 and/or HSP27 in the regulation of muscle mass
Fuminori Kawano1, Yoshikazu Matsuoka2, Yoshihiko Oke1, Yoko Higo3, Masahiro Terada2, XIAODONG WANG1, Naoya Nakai1, Hiroyuki Fukuda4, Shinobu Ohmi4, and Yoshinobu Ohira1*
1 Graduate School of Medicine, Osaka University, Toyonaka City, Osaka, Japan
2 Graduate School of Frontier Biosciences, Osaka University, Toyonaka City, Osaka, Japan
3 School of Science, Osaka University, Toyonaka City, Osaka, Japan
4 Institute of Medical Sciences, University of Tokyo, Minato-ku, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: ohira{at}space.hss.osaka-u.ac.jp.
Effects of 14 days of hindlimb unloading or synergist ablation-related overloading with or without deafferentation on the fiber cross-sectional area, myonuclear number, size, and domain, the number of nucleoli in a single myonucleus, and the levels in the phosphorylation of the ribosomal protein S6 (S6) and 27 kDa heat shock protein (HSP27) were studied in rat soleus. Hypertrophy of fibers (+24%), associated with increased nucleolar number (from 1-2 to 3-5) within a myonucleus and myonuclear domain (+27%) compared to the pre-experimental level, was induced by synergist ablation. Such phenomena were associated with increased levels of phosphorylated S6 (+84%) and HSP27 (+28%). Fiber atrophy (-52%), associated with decreased number (-31%) and domain size (-28%) of myonuclei and phosphorylation of S6 (-98%) and HSP27 (-63%), and with increased myonuclear size (+19%) and ubiquitination of MHC (+33%, p>0.05), was observed after unloading, which inhibited the mechanical load. Responses to deafferentation, which inhibited electromyogram level (-47%), were basically similar to those caused by hindlimb unloading, although the magnitudes were minor. The deafferentation-related responses were prevented and nucleolar number was even increased (+18%) by addition of synergist ablation, even though the integrated EMG level was still 30% less than controls. It is suggested that the load-dependent maintenance or upregulation of the nucleolar number and/or phosphorylation of S6 and HSP27 plays the important role(s) in the regulation of muscle mass. It was also indicated that such regulation was not necessarily associated with the neural activity.
