Role(s) of nucleoli and phosphorylation of ribosomal protein S6 and/or HSP27 in the regulation of muscle mass

Graduate Schools of 1 Medicine and 2 Frontier Biosciences and 3 School of Science, Osaka University, Suita City, Osaka; and 4 Institute of Medical Sciences, University of Tokyo, Minato-ku, Tokyo, Japan Submitted 30 May 2006 ; accepted in final form 15 December 2006 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 with the preexperimental 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 myosin heavy chain (+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 electromyogram 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. rat soleus muscle; functional overload; deafferentation; 27-kDa heat shock protein; ubiquitination of myosin heavy chain Address for reprint requests and other correspondence: Y. Ohira, Section of Applied Physiology, Graduate School of Medicine, Osaka Univ., Health and Sport Science Research Bldg., 1-17 Machikaneyama-cho, Toyonaka City, Osaka 560-0043, Japan (e-mail: ohira{at}space.hss.osaka-u.ac.jp )