Investigations in humans and animals over the last several years have shown exercise is a potent inhibitor of skeletal muscle wasting associated with diseases and experimental conditions resulting in glucocorticoid excess The mechanism of exercise is conserving muscle mass remains as yet unidentified. By examining hormone-responsive proteins as models for understanding protein regulation, the long-term objectives are to elucidate the molecular basis by which exercise prevents muscle atrophy from this state.
The specific aims are: (a) to determine whether exercise inhibits the up-regulation of glutamine synthetase enzyme induction and gene expression. (b) To evaluate whether exercise reverses the down-regulation of myosin and specifically myosin heavy chains. The parameters to be studied are myosin heavy chain synthesis and MRNA content, native isomyosin characterization, and the synthesis rates of each isoform. (c) Pathologic changes produced by glucocorticoids, besides those in myofibrillar proteins, are also found in the mitochondria. The use of CDNA probes for both a nuclear genome and a mitochondrial genome for the multisubunit cytochrome c oxidase, a mitochondrial marker enzyme, will allow us to identify whether there is a coordinated transcriptional response by exercise in preventing the mitochondrial alterations associated with muscle wasting, and will also provide evidence as to whether there is a predilection for myofibrillar or mitochondrial sparing in the prevention of atrophy by exercise. (d) Myofibrillar protein degradation will also be measured to fully comprehend the overall contributions of exercise in altering synthesis, degradation, or both in protein sparing. By comparing individual proteins, which are hormonally-regulated in opposing directions, basic knowledge can be obtained into whether the exercise-related interference of muscle atrophy is mediated preferentially through up-regulated or down-regulated proteins or both. By quantifying protein synthesis, enzyme induction, and gene expression, we will be able to assess the roles of transcriptional or translational control to these processes.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
Project #
Application #
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Illinois at Chicago
Other Specialized Schools
United States
Zip Code
Hickson, R C; Oehler, D T; Byerly, R J et al. (1997) Protective effect of glutamine from glucocorticoid-induced muscle atrophy occurs without alterations in circulating insulin-like growth factor (IGF)-I and IGF-binding protein levels. Proc Soc Exp Biol Med 216:65-71
Hickson, R C; Wegrzyn, L E; Osborne, D F et al. (1996) Glutamine interferes with glucocorticoid-induced expression of glutamine synthetase in skeletal muscle. Am J Physiol 270:E912-7
Hickson, R C; Wegrzyn, L E; Osborne, D F et al. (1996) Alanyl-glutamine prevents muscle atrophy and glutamine synthetase induction by glucocorticoids. Am J Physiol 271:R1165-72
Hickson, R C; Czerwinski, S M; Wegrzyn, L E (1995) Glutamine prevents downregulation of myosin heavy chain synthesis and muscle atrophy from glucocorticoids. Am J Physiol 268:E730-4
Marone, J R; Falduto, M T; Essig, D A et al. (1994) Effects of glucocorticoids and endurance training on cytochrome oxidase expression in skeletal muscle. J Appl Physiol 77:1685-90
Hickson, R C; Marone, J R (1993) Exercise and inhibition of glucocorticoid-induced muscle atrophy. Exerc Sport Sci Rev 21:135-67
Falduto, M T; Young, A P; Smyrniotis, G et al. (1992) Reduction of glutamine synthetase mRNA in hypertrophied skeletal muscle. Am J Physiol 262:R1131-6
Falduto, M T; Young, A P; Hickson, R C (1992) Exercise inhibits glucocorticoid-induced glutamine synthetase expression in red skeletal muscles. Am J Physiol 262:C214-20
Falduto, M T; Young, A P; Hickson, R C (1992) Exercise interrupts ongoing glucocorticoid-induced muscle atrophy and glutamine synthetase induction. Am J Physiol 263:E1157-63
Falduto, M T; Czerwinski, S M; Hickson, R C (1990) Glucocorticoid-induced muscle atrophy prevention by exercise in fast-twitch fibers. J Appl Physiol 69:1058-62

Showing the most recent 10 out of 13 publications