Cellular and molecular responses to increased skeletal muscle loading after irradiation.
Irradiation of rat skeletal muscles before increased loading has been shown to prevent compensatory hypertrophy for periods of up to 4 wk, possibly by preventing satellite cells from proliferating and providing new myonuclei. Recent work suggested that stem cell populations exist that might allow irradiated muscles to eventually hypertrophy over time. We report that irradiation essentially prevented hypertrophy in rat muscles subjected to 3 mo of functional overload (OL-Ir). The time course and magnitude of changes in cellular and molecular markers of anabolic and myogenic responses were similar in the OL-Ir and the contralateral nonirradiated, overloaded (OL) muscles for the first 3-7 days. These markers then returned to control levels in OL-Ir muscles while remaining elevated in OL muscles. The number of myonuclei and amount of DNA were increased markedly in OL but not OL-Ir muscles. Thus it appears that stem cells were not added to the irradiated muscles in this time period. These data are consistent with the theory that the addition of new myonuclei may be required for compensatory hypertrophy in the rat.
Adams
Gregory R
GR
Department of Physiology and Biophysics, Medical Sciences IC308, College of Medicine, University of California, Irvine, CA 92697, USA. gradams@UCI.edu
Caiozzo
Vincent J
VJ
Haddad
Fadia
F
Baldwin
Kenneth M
KM
D000222:Adaptation, Physiological / Q000528:radiation effects*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001835:Body Weight / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D002467:Cell Nucleus / Q000528:radiation effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D006614:Hindlimb; D006984:Hypertrophy / Q000517:prevention & control; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology* / Q000528:radiation effects*; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000528:radiation effects; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000528:radiation effects; D013314:Stress, Mechanical; D013995:Time
D015415:Biomarkers; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C503803:Myog protein, rat; D018008:Myogenin; D020033:Protein Isoforms; D012333:RNA, Messenger; D019938:Cyclin D1; D004247:DNA; D018995:Myosin Heavy Chains