| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Biomedical Sciences and Dalton Cardiovascular Research Center, University of Missouri-Columbia, Missouri 65211
2 Research Center for Genetic Medicine, Children’s National Medical Center, George Washington University, Washington, District of Columbia 20010
Physical inactivity and unloading lead to diverse skeletal muscle alterations. Our goal was to identify the genes in skeletal muscle whose expression is most sensitive to periods of unloading/reduced physical activity and that may be involved in triggering initial responses before phenotypic changes are evident. The ability of short periods of physical activity/loading as an effective countermeasure against changes in gene expression mediated by inactivity was also tested. Affymetrix microarrays were used to compare mRNA levels in the soleus muscle under three experimental treatments (n = 20–29 rats each): 12-h hindlimb unloading (HU), 12-h HU followed by 4 h of intermittent low-intensity ambulatory and postural activity (4-h reloading), and control (with ambulatory and postural activity). Using a combination of criteria, we identified a small set of genes (
1% of 8,738 genes on the array or 4% of significant expressed genes) with the most reproducible and largest responses to altered activity. Analysis revealed a coordinated regulation of transcription for a large number of key signaling proteins and transcription factors involved in protein synthesis/degradation and energy metabolism. Most (21 of 25) of the gene expression changes that were downregulated during HU returned at least to control levels during the reloading. In surprising contrast, 27 of 38 of the genes upregulated during HU remained significantly above control, but most showed trends toward reversal. This introduces a new concept that, in general, genes that are upregulated during unloading/inactivity will be more resistant to periodic reloading than those genes that are downregulated. This study reveals genes that are the most sensitive to loading/activity in rat skeletal muscle and indicates new targets that may initiate muscle alterations during inactivity.
microgravity; hindlimb suspension; exercise; aging; non-weight-bearing activity
This article has been cited by other articles:
|
|
 |
|
  E. E. Dupont-Versteegden, R. Nagarajan, M. L. Beggs, E. D. Bearden, P. M. Simpson, and C. A. Peterson Identification of cold-shock protein RBM3 as a possible regulator of skeletal muscle size through expression profiling Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1263 - R1273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Mazzatti, M. A. Smith, R. C. Oita, F.-L. Lim, A. J. White, and M. B. Reid Muscle unloading-induced metabolic remodeling is associated with acute alterations in PPAR{delta} and UCP-3 expression Physiol Genomics, July 1, 2008; 34(2): 149 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-W. Chen, C. M. Gregory, M. T. Scarborough, R. Shi, G. A. Walter, and K. Vandenborne Transcriptional pathways associated with skeletal muscle disuse atrophy in humans Physiol Genomics, November 14, 2007; 31(3): 510 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Hamilton, D. G. Hamilton, and T. W. Zderic Role of Low Energy Expenditure and Sitting in Obesity, Metabolic Syndrome, Type 2 Diabetes, and Cardiovascular Disease Diabetes, November 1, 2007; 56(11): 2655 - 2667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Sacheck, J.-P. K. Hyatt, A. Raffaello, R. T. Jagoe, R. R. Roy, V. R. Edgerton, S. H. Lecker, and A. L. Goldberg Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases FASEB J, January 1, 2007; 21(1): 140 - 155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Urso, A. G. Scrimgeour, Y.-W. Chen, P. D. Thompson, and P. M. Clarkson Analysis of human skeletal muscle after 48 h immobilization reveals alterations in mRNA and protein for extracellular matrix components J Appl Physiol, October 1, 2006; 101(4): 1136 - 1148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C C W Yu, A M Li, R C H So, A McManus, P C Ng, W Chu, D Chan, F Cheng, W K Chiu, C W Leung, et al. Longer term follow up of aerobic capacity in children affected by severe acute respiratory syndrome (SARS) Thorax, March 1, 2006; 61(3): 240 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. Zderic and M. T. Hamilton Physical inactivity amplifies the sensitivity of skeletal muscle to the lipid-induced downregulation of lipoprotein lipase activity J Appl Physiol, January 1, 2006; 100(1): 249 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Basterfield, J. M.H.M. Reul, and J. C. Mathers Impact of Physical Activity on Intestinal Cancer Development in Mice J. Nutr., December 1, 2005; 135(12): 3002S - 3008S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. DeRuisseau, R. A. Shanely, N. Akunuri, M. T. Hamilton, D. Van Gammeren, A. M. Zergeroglu, M. McKenzie, and S. K. Powers Diaphragm Unloading via Controlled Mechanical Ventilation Alters the Gene Expression Profile Am. J. Respir. Crit. Care Med., November 15, 2005; 172(10): 1267 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Liang and B. Ventura Physiological genomics in PG and beyond: July to September 2005 Physiol Genomics, October 17, 2005; 23(2): 119 - 124. [Full Text] [PDF]
|
|
|
|
|
|
T. Y. Kostrominova, D. E. Dow, R. G. Dennis, R. A. Miller, and J. A. Faulkner Comparison of gene expression of 2-mo denervated, 2-mo stimulated-denervated, and control rat skeletal muscles Physiol Genomics, July 14, 2005; 22(2): 227 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Selsby and S. L. Dodd Heat treatment reduces oxidative stress and protects muscle mass during immobilization Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2005; 289(1): R134 - R139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Stevenson, A. Koncarevic, P. G. Giresi, R. W. Jackman, and S. C. Kandarian Transcriptional profile of a myotube starvation model of atrophy J Appl Physiol, April 1, 2005; 98(4): 1396 - 1406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Jackman and S. C. Kandarian The molecular basis of skeletal muscle atrophy Am J Physiol Cell Physiol, October 1, 2004; 287(4): C834 - C843. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
