Gene expression during inactivity-induced muscle atrophy: effects of brief bouts of a forceful contraction countermeasure

• Published in: Journal of applied physiology (1985) Vol. 105; no. 4; pp. 1246 - 1254
• Main Authors: Kim, Soo J, Roy, Roland R, Kim, Jung A, Zhong, Hui, Haddad, Fadia, Baldwin, Kenneth M, Edgerton, V. Reggie
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.10.2008; American Physiological Society
• Subjects: Adaptation, Physiological; Animals; Biological and medical sciences; Disease Models, Animal; DNA - metabolism; Effects; Electric Stimulation Therapy; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Isometric Contraction; Metabolism; Muscle Proteins - biosynthesis; Muscle Proteins - genetics; Muscle Proteins - metabolism; Muscle, Skeletal - innervation; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Muscular Atrophy - genetics; Muscular Atrophy - metabolism; Muscular Atrophy - physiopathology; Muscular Atrophy - prevention & control; Muscular system; Organ Size; Protein Biosynthesis; Proteins; Rats; Rats, Sprague-Dawley; RNA - metabolism; Rodents; Signal Transduction; Spinal Cord Injuries - complications; Spinal Cord Injuries - genetics; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - physiopathology; Spinal Cord Injuries - therapy; Amyotrophy; inactivity; Stimulation; Gene expression; Insulin like growth factor 1; Striated muscle; Muscle contraction; atrogenes; electromechanical stimulation; Striated muscle disease; Vertebrata; Mammalia; IGF-1/PBK/Akt; skeletal muscle
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.90668.2008

1 Brain Research Institute and 2 Physiological Science Department, University of California, Los Angeles, Los Angeles; and 3 Department of Physiology and Biophysics, University of California, Irvine, Irvine, California Submitted 19 May 2008 ; accepted in final form 21 July 2008 Anabolic and catabolic markers of muscle protein metabolism were examined in inactivity-induced atrophying muscles with and without daily short-duration, high-resistance isometric contractions. Inactivity was achieved via spinal cord isolation (SI), which results in near inactivity of the hindlimb musculature without compromising the motoneuron-muscle connectivity. Adult rats were assigned to a control (Con) or SI group in which one limb was stimulated (SI-Stim, 5 consecutive days of brief bouts of high-load isometric contractions) while the other served as a SI control (SI). Both the medial gastrocnemius (MG) and soleus weights (relative to body weight) were 71% of Con in the SI, but maintained at Con in the SI-Stim group. Activity of the IGF-1/phosphatidylinositol 3-kinase (PI3K)/Akt pathway of protein synthesis was similar among all groups in the MG. Expression of atrogin-1 and muscle RING finger-1 (MuRF-1), markers of protein degradation, were higher in the MG and soleus of the SI than Con and maintained at Con in the SI-Stim. Compared with Con, the anti-growth factor myostatin was unaffected in the MG and soleus in the SI but was lower in the MG of the SI-Stim. These results demonstrate that upregulation of specific protein catabolic pathways plays a critical role in SI-induced atrophy, while this response was blunted by 4 min of daily high-resistance electromechanical stimulation and was able to preserve most of the muscle mass. Although the protein anabolic pathway (IGF-1/PI3K/Akt) appears to play a minor role in regulating mass in the SI model, increased translational capacity may have contributed to mass preservation in response to isometric contractions. inactivity; skeletal muscle; atrogenes; IGF-1/PI3K/Akt; electromechanical stimulation Address for reprint requests and other correspondence: R. R. Roy, Brain Research Institute, Univ. of California, Los Angeles, Box 951761, 1320 Gonda Neuroscience and Genetics Bldg., Los Angeles, CA 90095-1761 (e-mail: rrr{at}ucla.edu )