Isometric resistance exercise fails to counteract skeletal muscle atrophy processes during the initial stages of unloading.
This study tested the hypothesis that an isometric resistance training paradigm targeting the medial gastrocnemius of adult rodents is effective in preventing muscle atrophy during the early stages of hindlimb unloading by maintaining normal activation of the insulin receptor substrate-1 (IRS-1)/phosphoinositide-3 kinase (PI3K)/Akt signaling pathway. This pathway has been shown to simultaneously create an anabolic response while inhibiting processes upregulating catabolic processes involving expression of key enzymes in the ubiquitination of proteins for degradation. The findings show that during the 5 days of unloading 1) absolute medial gastrocnemius muscle weight reduction occurred by approximately 20%, but muscle weight corrected to body weight was not different from normal weight-bearing controls (P < 0.05); 2) normalized myofibril fraction concentration and content were decreased; and 3) a robust isometric training program, known to induce a hypertrophy response, failed to maintain the myofibril protein content. This response occurred despite fully blunting the increases in the mRNA for of atrogin-1, MURF-1, and myostatin, e.g., sensitive gene markers of an activated catabolic state. Analyses of the IRS-1/PI3K/Akt markers indicated that abundance of IRS-1 and phosphorylation state of Akt and p70S6 kinase were decreased relative to normal control rats, and the resistance training failed to maintain these signaling markers at normal regulatory level. Our findings suggest that to fully prevent muscle atrophy responses affecting the myofibril system during unloading, the volume of mechanical stress must be augmented sufficiently to maintain optimal activity of the IRS-1/PI3K/Akt pathway to provide an effective anabolic stimulus on the muscle.
Haddad
F
F
Dept. of Physiology and Biophysics, Univ. of California, Irvine, Irvine, CA 92697, USA. fhaddad@uci.edu
Adams
G R
GR
Bodell
P W
PW
Baldwin
K M
KM
D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005081:Exercise Therapy / Q000379:methods; D005260:Female; D019417:Hindlimb Suspension; D055504:Insulin Receptor Substrate Proteins; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D009210:Myofibrils / Q000378:metabolism; D055435:Myostatin; D009929:Organ Size; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D012584:Sciatic Nerve; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C525913:Mstn protein, rat; D009124:Muscle Proteins; D055435:Myostatin; D010750:Phosphoproteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000070584:Tripartite Motif Proteins; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt