Contraction-induced changes in TNFalpha and Akt-mediated signalling are associated with increased myofibrillar protein in rat skeletal muscle.
Resistance training results in skeletal muscle hypertrophy, but the molecular signalling mechanisms responsible for this altered phenotype are incompletely understood. We used a resistance training (RT) protocol consisting of three sessions [day 1 (d1), day 3 (d3), day 5 (d5)] separated by 48 h recovery (squat exercise, 4 sets x 10 repetitions, 3 min recovery) to determine early signalling responses to RT in rodent skeletal muscle. Six animals per group were killed 3 h after each resistance training session and 24 and 48 h after the last training session (d5). There was a robust increase in TNFalpha protein expression, and IKK(Ser180/181) and p38MAPK(Thr180/Tyr182) phosphorylation on d1 (P < 0.05), which abated with subsequent RT, returning to control levels by d5 for TNFalpha and IKK(Ser180/181). There was a trend for a decrease in MuRF-1 protein expression, 48 h following d5 of training (P = 0.08). Notably, muscle myofibrillar protein concentration was elevated compared to control 24 and 48 h following RT (P < 0.05). Akt(Ser473) and mTOR(Ser2448) phosphorylation were unchanged throughout RT. Phosphorylation of p70S6k(Thr389) increased 3 h post-exercise on d1, d3 and d5 (P < 0.05), whilst phosphorylation of S6(Ser235/236) increased on d1 and d3 (P < 0.05). Our results show a rapid attenuation of inflammatory signalling with repeated bouts of resistance exercise, concomitant with summation in translation initiation signalling in skeletal muscle. Indeed, the cumulative effect of these signalling events was associated with myofibrillar protein accretion, which likely contributes to the early adaptations in response to resistance training overload in the skeletal muscle.
Health Innovations Research Institute, School of Medical Science, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia.
Leonidas G
LG
Karagounis
Ben B
BB
Yaspelkis
Donald W
DW
Reeder
Graeme I
GI
Lancaster
John A
JA
Hawley
Vernon G
VG
Coffey
D000818:Animals; D051858:Forkhead Transcription Factors / Q000378:metabolism; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D023421:Models, Animal; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055070:Resistance Training; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D000071161:Forkhead Box Protein O1
D051858:Forkhead Transcription Factors; D020929:Mitogen-Activated Protein Kinase Kinases; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D051057:Proto-Oncogene Proteins c-akt; D044843:SKP Cullin F-Box Protein Ligases; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha; D044767:Ubiquitin-Protein Ligases; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C486692:Fbxo32 protein, rat; C499086:Trim63 protein, rat