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Reaction Kinetics Modeling of eHsp70 Induced by Norepinephrine in Response to Exercise StressFunding: This work was supported by Lendület grant LP 2015–6 of the Hungarian Academy of Sciences (A.L.) and the Higher Education Excellence Program of the Ministry of Human Capacities in the frame of Biotechnology research area of Budapest University of Technology and Economics (BME FIKP-BIO for A.L. and B.Sz.). Z. K. and M.K. were supported by the Nemzeti Bionika Program (ED_17–1–2017–0009). Hungarian National Research Foundation (OTKA K116525) financed C.S. and M.T. was supported by a GINOP-2.3.2.-15–2016–00047 grant.
Exercise elicits a systemic adaptation reaction, involving both neuroendocrine and cellular/paracrine stress responses, exemplified by the sympathoadrenergic activity and the release of cellular Hsp70 into the circulation. Regular sports training is known to result in increased fitness. In this study, we characterized the plasma norepinephrine and Hsp70 levels and modeled their relationship in response to exercise stress by bicycle ergometer in 12 trained judoka athletes and in 10 healthy controls. Resting norepinephrine was similar in both groups, whereas Hsp70 was significantly higher in controls compared to athletes. Intense exercise load induced both norepinephrine and Hsp70 elevation. However, both norepinephrine and Hsp70 were significantly lower in athletes compared to the control group. A reaction kinetic model was developed that provided a quantitative description of norepinephrine-facilitated extracellular Hsp70 release, congruent with the experimental data. Our study indicates that exercise-induced norepinephrine and extracellular Hsp70 may be coordinated responses to physiological stress, which are robustly affected by regular sports activity.
Received: 31 January 2020
Accepted: 01 July 2020
08 December 2020 (online)
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- 1 Zouhal H, Jacob C, Delamarche P. et al. Catecholamines and the effects of exercise, training and gender. Sports Med 2008; 38: 401-423 DOI: 10.2165/00007256-200838050-00004.
- 2 Wegele H, Muller L, Buchner J. Hsp70 and Hsp90 – a relay team for protein folding. Rev Physiol Biochem Pharmacol 2004; 151: 1-44. doi:10.1007/s10254-003-0021-1
- 3 Pockley AG, Henderson B. Extracellular cell stress (heat shock) proteins-immune responses and disease: An overview. Philos Trans R Soc Lond B Biol Sci 2018; 373: 20160522 doi:10.1098/rstb.2016.0522
- 4 Rosenzweig R, Nillegoda NB, Mayer MP. et al. The Hsp70 chaperone network. Nat Rev Mol Cell Biol 2019; 20: 665-680. DOI: 10.1038/s41580-019-0133-3.
- 5 Krepuska M, Szeberin Z, Sotonyi P. et al. Serum level of soluble Hsp70 is associated with vascular calcification. Cell Stress Chaperones 2011; 16: 257-265. DOI: 10.1007/s12192-010-0237-3.
- 6 Asea A. Initiation of the immune response by extracellular Hsp72: chaperokine activity of Hsp72. Curr Immunol Rev 2006; 2: 209-215. doi:10.2174/157339506778018514
- 7 Ren B, Zou G, Huang Y. et al. Serum levels of HSP70 and other DAMP proteins can aid in patient diagnosis after traumatic injury. Cell Stress Chaperones 2016; 21: 677-686 DOI: 10.1007/s12192-016-0694-4.
- 8 Heck TG, Scholer CM, de Bittencourt PI. HSP70 expression: does it a novel fatigue signalling factor from immune system to the brain?. Cell Biochem Funct 2011; 29: 215-226 doi:10.1002/cbf.1739
- 9 Johnson JD, Campisi J, Sharkey CM. et al. Adrenergic receptors mediate stress-induced elevations in extracellular Hsp72. J Appl Physiol (1985) 2005; 99: 1789-1795. DOI: 10.1152/japplphysiol.00390.2005.
- 10 Lilliefors HW. On the Kolmogorov-Smirnov test for normality with mean and variance unknown. J Am Stat Assoc 1967; 62: 399-402
- 11 Kemény Sándor DA, Kinga LaknéKomka, Péter Kunovszki. Kísérletek tervezése és értékelése. 2016
- 12 Bolla Marianna KA. Statisztikai következtetések elmélete. 2012
- 13 Harriss DJ, MacSween A, Atkinson G. Ethical standards in sport and exercise science research: 2020 update. Int J Sports Med 2019; 40: 813-817 doi:10.1055/a-1015-3123
- 14 Fleshner M, Johnson JD. Endogenous extra-cellular heat shock protein 72: releasing signal(s) and function. Int J Hyperthermia 2005; 21: 457-471. doi:10.1080/02656730500088211
- 15 Jodra P, Lago-Rodriguez A, Sanchez-Oliver AJ. et al. Effects of caffeine supplementation on physical performance and mood dimensions in elite and trained-recreational athletes. J Int Soc Sports Nutr 2020; 17: 2 DOI: 10.1186/s12970-019-0332-5.
- 16 Ruell PA, Simar D, Periard JD. et al. Plasma and lymphocyte Hsp72 responses to exercise in athletes with prior exertional heat illness. Amino Acids 2014; 46: 1491-1499. DOI: 10.1007/s00726-014-1721-3.
- 17 Yamada P, Amorim F, Moseley P. et al. Heat shock protein 72 response to exercise in humans. Sports Med 2008; 38: 715-733 DOI: 10.2165/00007256-200838090-00002.
- 18 Martinez de Toda I, De la Fuente M. The role of Hsp70 in oxi-inflamm-aging and its use as a potential biomarker of lifespan. Biogerontology 2015; 16: 709-721 doi:10.1007/s10522-015-9607-7
- 19 Alemi H, Khaloo P, Rabizadeh S. et al. Association of extracellular heat shock protein 70 and insulin resistance in type 2 diabetes; independent of obesity and C-reactive protein. Cell Stress Chaperones 2019; 24: 69-75. DOI: 10.1007/s12192-018-0942-x.
- 20 Jenei ZM, Gombos T, Forhecz Z. et al. Elevated extracellular HSP70 (HSPA1A) level as an independent prognostic marker of mortality in patients with heart failure. Cell Stress Chaperones 2013; 18: 809-813. DOI: 10.1007/s12192-013-0425-z.
- 21 Jenei ZM, Szeplaki G, Merkely B. et al. Persistently elevated extracellular HSP70 (HSPA1A) level as an independent prognostic marker in post-cardiac-arrest patients. Cell Stress Chaperones 2013; 18: 447-454. DOI: 10.1007/s12192-012-0399-2.
- 22 Magalhaes Fde C, Amorim FT, Passos RL. et al. Heat and exercise acclimation increases intracellular levels of Hsp72 and inhibits exercise-induced increase in intracellular and plasma Hsp72 in humans. Cell Stress Chaperones 2010; 15: 885-895. DOI: 10.1007/s12192-010-0197-7.
- 23 Giraldo E, Multhoff G, Ortega E. Noradrenaline increases the expression and release of Hsp72 by human neutrophils. Brain Behav Immun 2010; 24: 672-677 doi:10.1016/j.bbi.2010.02.003
- 24 Giraldo E, Hinchado MD, Ortega E. Combined activity of post-exercise concentrations of NA and eHsp72 on human neutrophil function: role of cAMP. J Cell Physiol 2013; 228: 1902-1906 doi:10.1002/jcp.24354
- 25 Fleshner M, Campisi J, Amiri L. et al. Cat exposure induces both intra- and extracellular Hsp72: the role of adrenal hormones. Psychoneuroendocrinology 2004; 29: 1142-1152. DOI: 10.1016/j.psyneuen.2004.01.007.
- 26 Whitham M, Walker GJ, Bishop NC. Effect of caffeine supplementation on the extracellular heat shock protein 72 response to exercise. J Appl Physiol (1985) 2006; 101: 1222-1227. doi:10.1152/japplphysiol.00409.2006
- 27 Ogawa K, Seta R, Shimizu T. et al. Plasma adenosine triphosphate and heat shock protein 72 concentrations after aerobic and eccentric exercise. Exerc Immunol Rev 2011; 17: 136-149
- 28 Nisoli E, Regianini L, Bulbarelli A. et al. Protective effects of noradrenaline against tumor necrosis factor-alpha-induced apoptosis in cultured rat brown adipocytes: Role of nitric oxide-induced heat shock protein 70 expression. Int J Obes Relat Metab Disord 2001; 25: 1421-1430. DOI: 10.1038/sj.ijo.0801788.
- 29 Iguchi M, Littmann AE, Chang SH. et al. Heat stress and cardiovascular, hormonal, and heat shock proteins in humans. J Athl Train 2012; 47: 184-190. DOI: 10.4085/1062-6050-47.2.184.
- 30 Hinchado MD, Giraldo E, Ortega E. Adrenoreceptors are involved in the stimulation of neutrophils by exercise-induced circulating concentrations of Hsp72: cAMP as a potential “intracellular danger signal”. J Cell Physiol 2012; 227: 604-608. doi:10.1002/jcp.22759
- 31 Protzner A, Szmodis M, Udvardy A. et al. Hormonal neuroendocrine and vasoconstrictor peptide responses of ball game and cyclic sport elite athletes by treadmill test. PLoS One 2015; 10: e0144691 DOI: 10.1371/journal.pone.0144691.