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The Exercise-Induced Stress Response of Skeletal Muscle, with Specific Emphasis on Humans

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Abstract

Skeletal muscle adapts to the stress of contractile activity via changes in gene expression to yield an increased content of a family of highly conserved cytoprotective proteins known as heat shock proteins (HSPs). These proteins function to maintain homeostasis, facilitate repair from injury and provide protection against future insults. The study of the exercise-induced production of HSPs in skeletal muscle is important for the exercise scientist as it may provide a valuable insight into the molecular mechanisms by which regular exercise can provide increased protection against related and non-related stressors. As molecular chaperones, HSPs are also fundamental in facilitating the cellular remodelling processes inherent to the training response.

Whilst the exercise-induced stress response of rodent skeletal muscle is relatively well characterized, data from humans are more infrequent and less insightful. Data indicate that acute endurance- and resistance-type exercise protocols increase the muscle content of ubiquitin, aB-crystallin, HSP27, HSP60, HSC70 and HSP70. Although increased HSP transcription occurs during exercise, immediately post-exercise or several hours following exercise, time-course studies using western blotting techniques have typically demonstrated a significant increase in protein content is only detectable within 1–2 days following the exercise stress. However, comparison amongst studies is complicated by variations in exercise protocol (mode, intensity, duration, damaging, non-damaging), muscle group examined, predominant HSP measured and, perhaps most importantly, differences in subject characteristics both within and between studies (training status, recent activity levels, nutritional status, age, sex, etc.). Following ‘non-damaging’ endurancetype activities (exercise that induces no overt structural and functional damage to the muscle), the stress response is thought to be mediated by redox signalling (transient and reversible oxidation of muscle proteins) as opposed to increases in contracting muscle temperature per se. Following ‘damaging’ forms of exercise (exercise that induces overt structural and functional damage to the muscle), the stress response is likely initiated by mechanical damage to protein structure and further augmented by the secondary damage associated with inflammatory processes occurring several days following the initial insult. Exercise training induces an increase in baseline HSP levels, which is dependent on a sustained and currently unknown dose of training and also on the individual’s initial training status. Furthermore, trained subjects display an attenuated or abolished stress response to customary exercise challenges, likely due to adaptations of baseline HSP levels and the antioxidant system.

Whilst further fundamental work is needed to accurately characterize the exercise-induced stress response in specific populations following varying exercise protocols, exercise scientists should also focus their efforts on elucidating the precise biological significance of the exercise-induced induction of HSPs. In addition to their potential cytoprotective properties, the role of HSPs in modulating cell signalling pathways related to both exercise adaptation and health and disease also needs further investigation. As a nonpharmacological intervention, exercise and the associated up-regulation of HSPs and the possible correction of maladapted pathways may therefore prove effective in providing protection against protein misfolding diseases and in preserving muscle function during aging.

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, 15-21 Webster Street, Liverpool, L3 2ET, UK

    James P. Morton & Barry Drust

  2. School of Clinical Sciences, University of Liverpool, Liverpool, UK

    Anna C. Kayani & Anne McArdle

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  1. James P. Morton
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  2. Anna C. Kayani
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Correspondence to James P. Morton.

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Morton, J.P., Kayani, A.C., McArdle, A. et al. The Exercise-Induced Stress Response of Skeletal Muscle, with Specific Emphasis on Humans. Sports Med 39, 643–662 (2009). https://doi.org/10.2165/00007256-200939080-00003

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