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Am J Physiol Regul Integr Comp Physiol 288: R1273-R1278, 2005; doi:10.1152/ajpregu.00688.2004
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ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY

Changes in PKB/Akt and calcineurin signaling during recovery in atrophied soleus muscle induced by unloading

Takao Sugiura,1 Noritaka Abe,1 Mai Nagano,1 Katsumasa Goto,2 Kunihiro Sakuma,3 Hisashi Naito,4 Toshitada Yoshioka,2,5 and Scott K. Powers6

1Department of Exercise and Health Sciences, Faculty of Education, Yamaguchi University, Yamaguchi; 2Department of Physiology, St. Marianna University School of Medicine, Miyamae, Kawasaki City, Kanagawa; 3Department of Legal Medicine, Kyoto Prefecture University of Medicine, Kyoto; 4Department of Exercise Physiology, School of Health and Sports Science, Juntendo University, Inba, Chiba; 5Hirosaki Gakuin University, Hirosaki, Aomori, Japan; and 6Department of Applied Physiology and Kinesiology, Center for Exercise Science, University of Florida, Gainesville, Florida

Submitted 6 October 2004 ; accepted in final form 20 December 2004

Protein kinase B [PKB, also known as Akt (PKB/Akt)] and calcineurin (CaN) are postulated to play important roles in integrating intracellular signaling in skeletal muscle in response to disuse and increased muscle loading. These experiments investigated changes in signal transduction of the downstream pathways of PKB/Akt and CaN during recovery following disuse-induced muscle atrophy. A 10-day period of hindlimb unloading (HLU) via tail suspension (male rats) was used to produce soleus muscle atrophy. Muscle recovery was achieved by returning animals to normal ambulation for 3–10 days. HLU resulted in significant muscle atrophy and a slow-to-fast fiber transition as revealed by appearance of type IId/x and IIb myosin heavy chain (MHC) isoforms. Muscle mass in HLU animals recovered to control (Con) levels after 10 days of reloading, but the fast-to-slow shift in muscle MHC was incomplete, as indicated by the continued presence of type IId/x MHC. Ten days of HLU resulted in a significant decrease (–43%) in muscle levels of phosphorylated PKB/Akt. In contrast, muscle levels of phosphorylated PKB/Akt were greater (+56%) in HLU than in Con animals early after the onset of reloading (3 days). Soleus levels of phosphorylated p70S6K were significantly higher (+26%) in HLU animals after 3 days of muscle reloading. Muscle levels of phosphorylated PKB/Akt and phosphorylated p70S6K returned to Con levels by day 10 of recovery. Moreover, muscle CaN levels were significantly higher than Con levels after 10 days of muscle reloading. These findings are consistent with the hypothesis that PKB/Akt and its downstream mediators are active in the regrowth of muscle mass during the early periods of recovery from muscle atrophy. Our data support the concept that CaN is involved in muscle remodeling during the later phases of recovery from disuse muscle atrophy.

regrowth; skeletal muscle; hindlimb unloading



Address for reprint requests and other correspondence: S. Powers, Dept. of Applied Physiology and Kinesiology, Center for Exercise Science, Univ. of Florida, Gainesville, FL 32611 (E-mail: spowers{at}hhp.ufl.edu




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