Gene expression during inactivity-induced muscle atrophy: effects of brief bouts of a forceful contraction countermeasure.
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 approximately 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.
Kim
Soo J
SJ
Brain Research Institute, University of California-Los Angeles, CA 90095-1761, USA.
Roy
Roland R
RR
Kim
Jung A
JA
Zhong
Hui
H
Haddad
Fadia
F
Baldwin
Kenneth M
KM
Edgerton
V Reggie
VR
D000222:Adaptation, Physiological; D000818:Animals; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy; D005260:Female; D007537:Isometric Contraction; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D009929:Organ Size; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy
D009124:Muscle Proteins; D012313:RNA; D004247:DNA