title: Rapid muscle atrophy response to unloading: pretranslational processes involving MHC and actin.
abstract: Skeletal muscles, especially weight-bearing muscles, are very sensitive to changes in loading state. The aim of this paper was to characterize the dynamic changes in the unloaded soleus muscle in vivo following a short bout of hindlimb suspension (HS), testing the hypothesis that transcriptional events respond early to the atrophic stimulus. In fact, we observed that after only 1 day of HS, primary transcript levels of skeletal alpha-actin and type I myosin heavy chain (MHC) genes were significantly reduced by more than 50% compared with ground control levels. The degree of the decline for the mRNA expression of actin and type I MHC lagged behind that of the pre-mRNA levels after 1 day of HS, but by 2 and 7 days of HS, large decreases were observed. Although the faster MHC isoforms, IIx and IIb, began to be expressed in soleus after 1 day of HS, a relatively significant shift in mRNA expression from the slow MHC isoform type I toward these fast MHC isoforms did not emerge until 7 days of HS. One day of HS was sufficient to show significant decreases in mRNA levels of putative signaling factors serum response factor (SRF), suppressor of cytokine signaling-3 (SOCS3), and striated muscle activator of Rho signaling (STARS), although transcription factors yin-yang-1 (YY1) and transcriptional enhancing factor-1 (TEF-1) were not significantly affected by HS. The protein levels of actin and type I MHC were significantly decreased after 2 days of HS, and SRF protein was significantly decreased after 7 days HS. Our results show that after only 1 day of unloading, pre-mRNA and mRNA expression of muscle proteins and muscle-specific signaling factors are significantly reduced, suggesting that the downregulation of the synthesis side of the protein balance equation that occurs in atrophying muscle is initiated rapidly.
authors.affiliation: Departmentof Physiology and Biophysics, Univ. of California, Irvine, D-346, Med. Sci. I, Irvine, CA 92697, USA. jmeehan@uci.edu
authors.forename: Julia M
authors.initials: JM
authors.lastname: Giger
authors.forename: Paul W
authors.initials: PW
authors.lastname: Bodell
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Baldwin
authors.forename: Fadia
authors.initials: F
authors.lastname: Haddad
mesh_terms: D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D019417:Hindlimb Suspension; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009210:Myofibrils / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size; D020033:Protein Isoforms; D012322:RNA Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026362:Serum Response Factor / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic; D050986:YY1 Transcription Factor / Q000235:genetics
chemical_list: D000199:Actins; D020033:Protein Isoforms; D012322:RNA Precursors; D012333:RNA, Messenger; D026362:Serum Response Factor; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D050986:YY1 Transcription Factor; C494700:Yy1 protein, rat; D018995:Myosin Heavy Chains