Temporal alterations in protein signaling cascades during recovery from muscle atrophy.
Currently, the repertoire of cellular and molecular pathways that control skeletal muscle atrophy and hypertrophy are not well defined. It is possible that intracellular regulatory signaling pathways are active at different times during the muscle hypertrophy process. The hypothesis of the given experiments was that cellular signals related to protein translation would be active at early time points of skeletal muscle regrowth, whereas transcriptional signals would be active at later time points of skeletal muscle regrowth. The phosphorylation status of p38 MAPK and JNK increased at the end of limb immobilization but returned to control values at recovery day 3. Transient increases in phosphorylation and in protein concentration occurred during recovery of soleus muscle mass. Phosphorylation of Akt, p70S6k, and signal transducer and activator of transcription 3 (STAT3) peaked on recovery day 3 compared with day 0. Glycogen synthase kinase (GSK)-3beta phosphorylation was increased on the sixth and fifteenth recovery day. In addition, transient peaks in seven protein concentrations occurred at different times of recovery: STAT3, calcineurin A (CaNA), CaNB, and beta4E-BP1 protein concentrations peaked on the third recovery day; p70S6k, STAT3, Akt, and GSK3-beta peaked on the sixth recovery day; and GSK3-beta peaked on the fifteenth recovery day. The apexes of STAT3 and GSK3-beta protein concentrations remained elevated for two recovery time points. Thus the time course of increase in molecules of signaling pathways differed as the young rat soleus muscle regrew from an atrophied state.
Childs
Thomas E
TE
Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
Spangenburg
Espen E
EE
Vyas
Dharmesh R
DR
Booth
Frank W
FW
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006984:Hypertrophy / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism* / Q000503:physiopathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000503:physiopathology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011930:Reaction Time / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; C494920:Akt1 protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3