Details

Autor(en) / Beteiligte

• Allen, David L
• Bandstra, Eric R
• Harrison, Brooke C
• Thorng, Seiha
• Stodieck, Louis S
• Kostenuik, Paul J
• Morony, Sean
• Lacey, David L
• Hammond, Timothy G
• Leinwand, Leslie L
• Argraves, W. Scott
• Bateman, Ted A
• Barth, Jeremy L

Titel

Effects of spaceflight on murine skeletal muscle gene expression

Ist Teil von

• Journal of applied physiology (1985), 2009-02, Vol.106 (2), p.582-595

Ort / Verlag

Bethesda, MD: Am Physiological Soc

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

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