Journal of Applied Physiology AJP: Heart and Circulatory Physiology
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J Appl Physiol 106: 582-595, 2009. First published December 12, 2008; doi:10.1152/japplphysiol.90780.2008
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Effects of spaceflight on murine skeletal muscle gene expression

David L. Allen,1 Eric R. Bandstra,2 Brooke C. Harrison,3 Seiha Thorng,4 Louis S. Stodieck,5 Paul J. Kostenuik,6 Sean Morony,6 David L. Lacey,6 Timothy G. Hammond,7,8 Leslie L. Leinwand,3 W. Scott Argraves,4 Ted A. Bateman,2 and Jeremy L. Barth4

1Department of Integrative Physiology, University of Colorado, Boulder, Colorado; 2Department of Bioengineering, Clemson University, Clemson, South Carolina; 3Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado; 4Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina; 5BioServe Space Technologies, University of Colorado, Boulder, Colorado; 6Metabolic Disorders, Amgen Inc., Thousand Oaks, California; 7Nephrology Division, Duke University School of Medicine, Durham, North Carolina; and 8Durham Veteran Affairs Medical Center, Durham, North Carolina

Submitted 17 June 2008 ; accepted in final form 10 December 2008

Spaceflight results in a number of adaptations to skeletal muscle, including atrophy and shifts toward faster muscle fiber types. To identify changes in gene expression that may underlie these adaptations, we used both microarray expression analysis and real-time polymerase chain reaction to quantify shifts in mRNA levels in the gastrocnemius from mice flown on the 11-day, 19-h STS-108 shuttle flight and from normal gravity controls. Spaceflight data also were compared with the ground-based unloading model of hindlimb suspension, with one group of pure suspension and one of suspension followed by 3.5 h of reloading to mimic the time between landing and euthanization of the spaceflight mice. Analysis of microarray data revealed that 272 mRNAs were significantly altered by spaceflight, the majority of which displayed similar responses to hindlimb suspension, whereas reloading tended to counteract these responses. Several mRNAs altered by spaceflight were associated with muscle growth, including the phosphatidylinositol 3-kinase regulatory subunit p85{alpha}, insulin response substrate-1, the forkhead box O1 transcription factor, and MAFbx/atrogin1. Moreover, myostatin mRNA expression tended to increase, whereas mRNA levels of the myostatin inhibitor FSTL3 tended to decrease, in response to spaceflight. In addition, mRNA levels of the slow oxidative fiber-associated transcriptional coactivator peroxisome proliferator-associated receptor (PPAR)-{gamma} coactivator-1{alpha} and the transcription factor PPAR-{alpha} were significantly decreased in spaceflight gastrocnemius. Finally, spaceflight resulted in a significant decrease in levels of the microRNA miR-206. Together these data demonstrate that spaceflight induces significant changes in mRNA expression of genes associated with muscle growth and fiber type.

atrophy; hindlimb suspension; microRNA; myostatin


Address for reprint requests and other correspondence: J. L. Barth, Dept. of Cell Biology and Anatomy, Medical Univ. of South Carolina, Charleston, SC 29425 (e-mail: barthj{at}musc.edu)




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