Skip to main content
SpringerLink
Log in

Potential Cytoprotective Effects of Heat Shock Proteins to Skeletal Muscle

  • Chapter
Heat Shock Protein-Based Therapies

Part of the book series: Heat Shock Proteins ((HESP,volume 9))

Abstract

Heat shock proteins (HSP) are chaperone molecules that are known to facilitate protein synthesis, protein assembly, provide cellular protection and regulate intracellular signaling. These cytoprotective effects have been linked to increases in HSP70 and HSP27p concentrations but there has been little progress in determining the specific role of HSP in human skeletal muscle adaptations. Short wave diathermy (SWD) and ultrasound are treatments commonly used to stimulate deep heat increases in skeletal muscle with limited research examining the effects of increased muscle temperature on muscle damage induced injury severity. Current research cannot definitively identify the mechanistic roles of HSP in mitigation of muscle damage even though they are commonly cited as mechanism of action for prevention of damage in heat-treated muscle. This article will examine the role of HSP induction in skeletal muscle as a therapeutic countermeasure for reduction of muscle atrophy during prolonged periods of immobilization as well as mechanisms for accelerated repair of injured muscle fibers through increased total protein concentrations.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

HSF-1:

Heat shock transcription factor-1

HSFs:

Heat shock factors

HSP:

Heat shock proteins

HSP70:

70-kDa HSP

HSP72:

70-kDa HSP

IL:

Interleukin

SOL:

Soleus

References

  1. Hough T (1902) Ergographic studies in muscular soreness. Am J Physiol 7:76–92

    Google Scholar 

  2. Armstrong RB (1990) Initial events in exercise-induced muscular injury. Med Sci Sports Exerc 22:429–435

    Article  CAS  PubMed  Google Scholar 

  3. Proske U, Morgan DL (2001) Muscle damage from eccentric exercise: mechanism, mechanical signs, adaptation and clinical applications. J Physiol 537:333–345

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Warren GL, Lowe DA, Hayes DA, Farmer MA, Armstrong RB (1995) Redistribution of cell membrane probes following contraction-induced injury of mouse soleus muscle. Cell Tissue Res 282:311–320

    Article  CAS  PubMed  Google Scholar 

  5. Belcastro AN, Shewchuk LD, Raj DA (1998) Exercise-induced muscle injury: a calpain hypothesis. Mol Cell Biochem 179:135–145

    Article  CAS  PubMed  Google Scholar 

  6. Friden J, Lieber RL (1996) Ultrastructural evidence for loss of calcium homeostasis in exercised skeletal muscle. Acta Physiol Scand 158:381–382

    Article  CAS  PubMed  Google Scholar 

  7. Armstrong RB, Ogilvie RW, Schwane JA (1983) Eccentric exercise-induced injury to rat skeletal muscle. J Appl Physiol Respir Environ Exerc Physiol 54:80–93

    CAS  PubMed  Google Scholar 

  8. Friden J, Kjorell U, Thornell LE (1984) Delayed muscle soreness and cytoskeletal alterations: an immunocytological study in man. Int J Sports Med 5:15–18

    Article  CAS  PubMed  Google Scholar 

  9. Newham DJ, McPhail G, Mills KR, Edwards RH (1983) Ultrastructural changes after concentric and eccentric contractions of human muscle. J Neurol Sci 61:109–122

    Article  CAS  PubMed  Google Scholar 

  10. Stauber WT (1989) Eccentric action of muscles: physiology, injury, and adaptation. Exerc Sport Sci Rev 17:157–185

    CAS  PubMed  Google Scholar 

  11. Boppart MD, Aronson D, Gibson L, Roubenoff R, Abad LW, Bean J, Goodyear LJ, Fielding RA (1999) Eccentric exercise markedly increases c-Jun NH(2)-terminal kinase activity in human skeletal muscle. J Appl Physiol (1985) 87:1668–1673

    CAS  Google Scholar 

  12. Maglara AA, Vasilaki A, Jackson MJ, McArdle A (2003) Damage to developing mouse skeletal muscle myotubes in culture: protective effect of heat shock proteins. J Physiol 548:837–846

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Thompson HS, Maynard EB, Morales ER, Scordilis SP (2003) Exercise-induced HSP27, HSP70 and MAPK responses in human skeletal muscle. Acta Physiol Scand 178:61–72

    Article  CAS  PubMed  Google Scholar 

  14. Jackman RW, Kandarian SC (2004) The molecular basis of skeletal muscle atrophy. Am J Physiol Cell Physiol 287:C834–C843

    Article  CAS  PubMed  Google Scholar 

  15. Venojarvi M, Kvist M, Jozsa L, Kalimo H, Hanninen O, Atalay M (2007) Skeletal muscle HSP expression in response to immobilization and remobilization. Int J Sports Med 28:281–286

    Article  CAS  PubMed  Google Scholar 

  16. Martineau LC, Gardiner PF (2001) Insight into skeletal muscle mechanotransduction: MAPK activation is quantitatively related to tension. J Appl Physiol (1985) 91:693–702

    CAS  Google Scholar 

  17. Bartlett JD, Close GL, Drust B, Morton JP (2014) The emerging role of p53 in exercise metabolism. Sports Med 44:303–309

    Article  PubMed  Google Scholar 

  18. Biral D, Jakubiec-Puka A, Ciechomska I, Sandri M, Rossini K, Carraro U, Betto R (2000) Loss of dystrophin and some dystrophin-associated proteins with concomitant signs of apoptosis in rat leg muscle overworked in extension. Acta Neuropathol 100:618–626

    Article  CAS  PubMed  Google Scholar 

  19. Thompson HS, Clarkson PM, Scordilis SP (2002) The repeated bout effect and heat shock proteins: intramuscular HSP27 and HSP70 expression following two bouts of eccentric exercise in humans. Acta Physiol Scand 174:47–56

    Article  CAS  PubMed  Google Scholar 

  20. Thompson HS, Scordilis SP, Clarkson PM, Lohrer WA (2001) A single bout of eccentric exercise increases HSP27 and HSC/HSP70 in human skeletal muscle. Acta Physiol Scand 171:187–193

    Article  CAS  PubMed  Google Scholar 

  21. Bombardier E, Vigna C, Iqbal S, Tiidus PM, Tupling AR (2009) Effects of ovarian sex hormones and downhill running on fiber-type-specific HSP70 expression in rat soleus. J Appl Physiol (1985) 106:2009–2015

    Article  CAS  Google Scholar 

  22. Oishi Y, Taniguchi K, Matsumoto H, Ishihara A, Ohira Y, Roy RR (2002) Muscle type-specific response of HSP60, HSP72, and HSC73 during recovery after elevation of muscle temperature. J Appl Physiol (1985) 92:1097–1103

    Article  CAS  Google Scholar 

  23. Touchberry CD, Gupte AA, Bomhoff GL, Graham ZA, Geiger PC, Gallagher PM (2012) Acute heat stress prior to downhill running may enhance skeletal muscle remodeling. Cell Stress Chaperones 17:693–705

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Hooper PL, Hooper JJ (2005) Loss of defense against stress: diabetes and heat shock proteins. Diabetes Technol Ther 7:204–208

    Article  CAS  PubMed  Google Scholar 

  25. Soti C, Nagy E, Giricz Z, Vigh L, Csermely P, Ferdinandy P (2005) Heat shock proteins as emerging therapeutic targets. Br J Pharmacol 146:769–780

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Kregel KC (2002) Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J Appl Physiol (1985) 92:2177–2186

    Article  CAS  Google Scholar 

  27. Gjovaag TF, Dahl HA (2006) Effect of training and detraining on the expression of heat shock proteins in m. triceps brachii of untrained males and females. Eur J Appl Physiol 98:310–322

    Article  CAS  PubMed  Google Scholar 

  28. Gjovaag TF, Vikne H, Dahl HA (2006) Effect of concentric or eccentric weight training on the expression of heat shock proteins in m. biceps brachii of very well trained males. Eur J Appl Physiol 96:355–362

    Article  CAS  PubMed  Google Scholar 

  29. Koh TJ, Brooks SV (2001) Lengthening contractions are not required to induce protection from contraction-induced muscle injury. Am J Physiol Regul Integr Comp Physiol 281:R155–R161

    CAS  PubMed  Google Scholar 

  30. Koh TJ, Escobedo J (2004) Cytoskeletal disruption and small heat shock protein translocation immediately after lengthening contractions. Am J Physiol Cell Physiol 286:C713–C722

    Article  CAS  PubMed  Google Scholar 

  31. Willoughby DS, Rosene J, Myers J (2003) HSP-72 and ubiquitin expression and caspase-3 activity after a single bout of eccentric exercise. J Exerc Physiol Online 6:96–104

    Google Scholar 

  32. Liu Y, Steinacker JM (2001) Changes in skeletal muscle heat shock proteins: pathological significance. Front Biosci 6:D12–D25

    Article  CAS  PubMed  Google Scholar 

  33. Ingalls CP, Warren GL, Armstrong RB (1998) Dissociation of force production from MHC and actin contents in muscles injured by eccentric contractions. J Muscle Res Cell Motil 19:215–224

    Article  CAS  PubMed  Google Scholar 

  34. Welc SS, Judge AR, Clanton TL (2013) Skeletal muscle interleukin-6 regulation in hyperthermia. Am J Physiol Cell Physiol 305:C406–C413

    Article  CAS  PubMed  Google Scholar 

  35. Miyabara EH, Martin JL, Griffin TM, Moriscot AS, Mestril R (2006) Overexpression of inducible 70-kDa heat shock protein in mouse attenuates skeletal muscle damage induced by cryolesioning. Am J Physiol Cell Physiol 290:C1128–C1138

    Article  CAS  PubMed  Google Scholar 

  36. Nosaka K, Muthalib M, Lavender A, Laursen PB (2007) Attenuation of muscle damage by preconditioning with muscle hyperthermia 1-day prior to eccentric exercise. Eur J Appl Physiol 99:183–192

    Article  CAS  PubMed  Google Scholar 

  37. Mayer MP, Bukau B (2005) Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62:670–684

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Lepore DA, Hurley JV, Stewart AG, Morrison WA, Anderson RL (2000) Prior heat stress improves survival of ischemic-reperfused skeletal muscle in vivo. Muscle Nerve 23:1847–1855

    Article  CAS  PubMed  Google Scholar 

  39. McArdle A, Dillmann WH, Mestril R, Faulkner JA, Jackson MJ (2004) Overexpression of HSP70 in mouse skeletal muscle protects against muscle damage and age-related muscle dysfunction. FASEB J 18:355–357

    CAS  PubMed  Google Scholar 

  40. Kojima A, Goto K, Morioka S, Naito T, Akema T, Fujiya H, Sugiura T, Ohira Y, Beppu M, Aoki H, Yoshioka T (2007) Heat stress facilitates the regeneration of injured skeletal muscle in rats. J Orthop Sci 12:74–82

    Article  PubMed  Google Scholar 

  41. Lawler JM, Song W, Kwak HB (2006) Differential response of heat shock proteins to hindlimb unloading and reloading in the soleus. Muscle Nerve 33:200–207

    Article  CAS  PubMed  Google Scholar 

  42. Oishi Y, Taniguchi K, Matsumoto H, Kawano F, Ishihara A, Ohira Y (2003) Upregulation of HSP72 in reloading rat soleus muscle after prolonged hindlimb unloading. Jpn J Physiol 53:281–286

    Article  CAS  PubMed  Google Scholar 

  43. Selsby JT, Rother S, Tsuda S, Pracash O, Quindry J, Dodd SL (2007) Intermittent hyperthermia enhances skeletal muscle regrowth and attenuates oxidative damage following reloading. J Appl Physiol (1985) 102:1702–1707

    Article  CAS  Google Scholar 

  44. Goto K, Okuyama R, Sugiyama H, Honda M, Kobayashi T, Uehara K, Akema T, Sugiura T, Yamada S, Ohira Y, Yoshioka T (2003) Effects of heat stress and mechanical stretch on protein expression in cultured skeletal muscle cells. Pflugers Arch 447:247–253

    Article  CAS  PubMed  Google Scholar 

  45. Kobayashi T, Goto K, Kojima A, Akema T, Uehara K, Aoki H, Sugiura T, Ohira Y, Yoshioka T (2005) Possible role of calcineurin in heating-related increase of rat muscle mass. Biochem Biophys Res Commun 331:1301–1309

    Article  CAS  PubMed  Google Scholar 

  46. Goto K, Honda M, Kobayashi T, Uehara K, Kojima A, Akema T, Sugiura T, Yamada S, Ohira Y, Yoshioka T (2004) Heat stress facilitates the recovery of atrophied soleus muscle in rat. Jpn J Physiol 54:285–293

    Article  CAS  PubMed  Google Scholar 

  47. Meriin AB, Yaglom JA, Gabai VL, Zon L, Ganiatsas S, Mosser DD, Zon L, Sherman MY (1999) Protein-damaging stresses activate c-Jun N-terminal kinase via inhibition of its dephosphorylation: a novel pathway controlled by HSP72. Mol Cell Biol 19:2547–2555

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Wong YM, La Porte HM, Szilagyi A, Bach HH, Ke-He L, Kennedy RH, Gamelli RL, Shankar R, Majetschak M (2014) Activities of nonlysosomal proteolytic systems in skeletal and cardiac muscle during burn-induced hypermetabolism. J Burn Care Res 35:319–327

    Article  PubMed Central  PubMed  Google Scholar 

  49. Kerksick CM, Kreider RB, Willoughby DS (2010) Intramuscular adaptations to eccentric exercise and antioxidant supplementation. Amino Acids 39:219–232

    Article  CAS  PubMed  Google Scholar 

  50. Du J, Wang X, Miereles C, Bailey JL, Debigare R, Zheng B, Price SR, Mitch WE (2004) Activation of caspase-3 is an initial step triggering accelerated muscle proteolysis in catabolic conditions. J Clin Invest 113:115–123

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Lee SW, Dai G, Hu Z, Wang X, Du J, Mitch WE (2004) Regulation of muscle protein degradation: coordinated control of apoptotic and ubiquitin-proteasome systems by phosphatidylinositol 3 kinase. J Am Soc Nephrol 15:1537–1545

    Article  CAS  PubMed  Google Scholar 

  52. Beere HM (2005) Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways. J Clin Invest 115:2633–2639

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Naito H, Powers SK, Demirel HA, Sugiura T, Dodd SL, Aoki J (2000) Heat stress attenuates skeletal muscle atrophy in hindlimb-unweighted rats. J Appl Physiol (1985) 88:359–363

    CAS  Google Scholar 

  54. Touchberry C, Le T, Richmond S, Prewitt M, Beck D, Carr D, Vardiman P, Gallagher P (2008) Diathermy treatment increases heat shock protein expression in female, but not male skeletal muscle. Eur J Appl Physiol 102:319–323

    Article  CAS  PubMed  Google Scholar 

  55. Ogura Y, Naito H, Tsurukawa T, Ichinoseki-Sekine N, Saga N, Sugiura T, Katamoto S (2007) Microwave hyperthermia treatment increases heat shock proteins in human skeletal muscle. Br J Sports Med 41:453–455, discussion 455

    Article  PubMed Central  PubMed  Google Scholar 

  56. Neef DW, Jaeger AM, Thiele DJ (2011) Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases. Nat Rev Drug Discov 10:930–944

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Hargitai J, Lewis H, Boros I, Racz T, Fiser A, Kurucz I, Benjamin I, Vigh L, Penzes Z, Csermely P, Latchman DS (2003) Bimoclomol, a heat shock protein co-inducer, acts by the prolonged activation of heat shock factor-1. Biochem Biophys Res Commun 307:689–695

    Article  CAS  PubMed  Google Scholar 

  58. Vigh L, Literati PN, Horvath I, Torok Z, Balogh G, Glatz A, Kovacs E, Boros I, Ferdinandy P, Farkas B, Jaszlits L, Jednakovits A, Koranyi L, Maresca B (1997) Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects. Nat Med 3:1150–1154

    Article  CAS  PubMed  Google Scholar 

  59. Nanasi PP, Jednakovits A (2001) Multilateral in vivo and in vitro protective effects of the novel heat shock protein coinducer, bimoclomol: results of preclinical studies. Cardiovasc Drug Rev 19:133–151

    Article  CAS  PubMed  Google Scholar 

  60. Kalmar B, Edet-Amana E, Greensmith L (2012) Treatment with a coinducer of the heat shock response delays muscle denervation in the SOD1-G93A mouse model of amyotrophic lateral sclerosis. Amyotroph Lateral Scler 13:378–392

    Article  CAS  PubMed  Google Scholar 

  61. Kalmar B, Lu CH, Greensmith L (2014) The role of heat shock proteins in amyotrophic lateral sclerosis: the therapeutic potential of arimoclomol. Pharmacol Ther 141:40–54

    Article  CAS  PubMed  Google Scholar 

  62. Cudkowicz ME, Shefner JM, Simpson E, Grasso D, Yu H, Zhang H, Shui A, Schoenfeld D, Brown RH, Wieland S, Barber JR, Northeast ALSC (2008) Arimoclomol at dosages up to 300 mg/day is well tolerated and safe in amyotrophic lateral sclerosis. Muscle Nerve 38:837–844

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the following individuals for their research and technical assistance: Chad Touchberry, Anisha Gupte, Gregory Bomhoff, Zachary Graham, Paige Geiger, Tung Le, Scott Richmond, Michael Prewitt, David Beck, and David Carr. This work was supported in part by General Research Fund awards from the University of Kansas to Philip Gallagher and Phillip Vardiman respectively. This research was also partially funded by a research award from the Mid America Athletic Trainers’ Association to Phillip Vardiman.

Author information

Authors and Affiliations

  1. Applied Physiology Lab, Department of Health, Sport, and Exercise Sciences, University of Kansas, 1301 Sunnyside Ave, Rm 161, Lawrence, KS, 66045, USA

    John P. Vardiman, Philip M. Gallagher & Jacob A. Siedlik

Authors
  1. John P. Vardiman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philip M. Gallagher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jacob A. Siedlik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John P. Vardiman .

Editor information

Editors and Affiliations

  1. Professor and VD for Research Innovations, Deanship for Scientific Research,, University of Dammam, Dammam, Saudi Arabia

    Alexzander A.A. Asea

  2. Deanship for Scientific Research and Preventive Dental Sciences Department, College of Dentistry, University of Dammam, Dammam, Saudi Arabia

    Naif N. Almasoud

  3. Gastrointestinal Translational Research, Center for Radiation Oncology Research, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Sunil Krishnan

  4. Department of Microbiology, Immunology & Biochemistry, Morehouse School of Medicine, Atlanta, Georgia, USA

    Punit Kaur

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Vardiman, J.P., Gallagher, P.M., Siedlik, J.A. (2015). Potential Cytoprotective Effects of Heat Shock Proteins to Skeletal Muscle. In: Asea, A., Almasoud, N., Krishnan, S., Kaur, P. (eds) Heat Shock Protein-Based Therapies. Heat Shock Proteins, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-319-17211-8_7

Download citation

Publish with us

Policies and ethics

Search

Navigation