Rapid muscle atrophy response to unloading: pretranslational processes involving MHC and actin

Department of Physiology and Biophysics, University of California, Irvine, California Submitted 31 March 2009 ; accepted in final form 10 July 2009 Skeletal muscles, especially weight-bearing muscles, are very sensitive to changes in loading state. The aim of this paper was to characterize the dynam...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of applied physiology (1985) 2009-10, Vol.107 (4), p.1204-1212
Hauptverfasser: Giger, Julia M, Bodell, Paul W, Zeng, Ming, Baldwin, Kenneth M, Haddad, Fadia
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Department of Physiology and Biophysics, University of California, Irvine, California Submitted 31 March 2009 ; accepted in final form 10 July 2009 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 -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. myosin heavy chain; skeletal -actin; hindlimb suspension; soleus muscle; SOCS3; SRF; STARS Address for reprint requests and other correspondence: J. M. Giger, Dept.of Physiology and Biophysics, Univ. of California, Irvine, D-346, Med. Sci. I, Irvine, CA 92697 (e-mail: jmeehan{at}uci.edu ).
ISSN:8750-7587
1522-1601
DOI:10.1152/japplphysiol.00344.2009