Abstract
Heat acclimation (HA) in humans promotes thermoregulatory adaptations that support management of core temperature in hot environments and reduces the likelihood of heat related illness. Another adaptation to HA is thermotolerance through induction of the heat shock protein (HSP) stress system, which provides protection against thermal insult. However, whether or not HA leads to upregulation of the intracellular HSP system, namely intracellular HSP70 (HSP70), is unclear in humans. Therefore, the purposes of this meta-analysis were to determine if HA leads to HSP70 induction among humans and to evaluate how methodological differences among HA studies influence findings regarding HA-induced HSP70 accumulation. Several databases were searched to identify studies that measured HSP70 (protein and mRNA) changes in response to HA among humans. The effect of HA on HSP70 was analyzed. Differences in the effect of HA were assessed between protein and mRNA. The moderating effect of several independent variables (HA frequency, HA duration, core temperature, exercise intensity) on HSP70 was also evaluated. Data were extracted from 12 studies including 118 participants (mean age 24 years, 98% male). There was a significant effect of HA on HSP70 expression, g = 0.97 (95% CI, 0.08–1.89). The effect of HA was different between subgroups (protein vs. mRNA), g = 1.51 (95% CI, 0.71–2.31), and g = − 0.39 (95% CI, − 1.36), respectively. The frequency of HA (in days) moderated HSP70 protein expression. There was a significant effect of heat acclimation on HSP70 induction in humans. The only factor among identified studies that may moderate this response was the frequency (number of days) of heat exposure.
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Amorim F, Yamada P, Robergs R, Schneider S, Moseley P (2011) Effects of whole-body heat acclimation on cell injury and cytokine responses in peripheral blood mononuclear cells. Eur J Appl Physiol 111:1609–1618. https://doi.org/10.1007/s00421-010-1780-4
Amorim FT, Fonseca IT, Machado-Moreira CA, de Magalhães F, C (2015) Insights into the role of heat shock protein 72 to whole-body heat acclimation in humans. Temperature. https://doi.org/10.1080/23328940.2015.1110655
Anckar J, Sistonen L (2011) Regulation of HSF1 function in the heat stress response: implications in aging and disease. Annu Rev Biochem. https://doi.org/10.1146/annurev-biochem-060809-095203
Armed Forces Health Surveillance Branch (2019) Update: heat illness, active component, U.S. Armed Forces, 2018. MSMR
Armstrong LE, Casa DJ, Millard-Stafford M et al (2007) Exertional heat illness during training and competition. Med Sci Sports Exerc. https://doi.org/10.1249/MSS.0b013e31802fa199
Beaudin AE, Clegg ME, Walsh ML, White MD (2009) Adaptation of exercise ventilation during an actively-induced hyperthermia following passive heat acclimation. Am J Physiol Integr Comp Physiol. https://doi.org/10.1152/ajpregu.90672.2008
Beckham JT, Wilmink GJ, Mackanos MA et al (2008) Role of HSP70 in cellular thermotolerance. Lasers Surg Med. https://doi.org/10.1002/lsm.20713
Bittencourt A, Porto RR (2017) eHSP70/iHSP70 and divergent functions on the challenge: effect of exercise and tissue specificity in response to stress. Clin Physiol Funct Imaging
Brazaitis M, Skurvydas A (2010) Heat acclimation does not reduce the impact of hyperthermia on central fatigue. Eur J Appl Physiol 109:771–778. https://doi.org/10.1007/s00421-010-1429-3
Campisi J, Leem TH, Fleshner M (2003) Stress-induced extracellular Hsp72 is a functionally significant danger signal to the immune system. Cell Stress Chaperones. https://doi.org/10.1379/1466-1268(2003)008<0272:SEHIAF>2.0.CO;2
Carter R, Cheuvront SN, Williams JO et al (2005) Epidemiology of hospitalizations and deaths from heat illness in soldiers. Med Sci Sports Exerc. https://doi.org/10.1249/01.mss.0000174895.19639.ed
Casa DJ, Armstrong LE, Ganio MS, Yeargin SW (2005) Exertional heat stroke in competitive athletes. Curr Sports Med Rep. https://doi.org/10.1097/01.CSMR.0000306292.64954.da
Chen HW, Kuo HT, Wang SJ et al (2005) In vivo heat shock protein assembles with septic liver NF-κB/I- κB complex regulating NF-κB activity. Shock. https://doi.org/10.1097/01.shk.0000174020.87439.f2
Craig EA, Weissman JS, Horwich AL (1994) Heat shock proteins and molecular chaperones: mediators of protein conformation and turnover in the cell. Cell
Day JR, Rossiter HB, Coats EM et al (2003) The maximally attainable V̇O2 during exercise in humans: the peak vs. maximum issue. J Appl Physiol. https://doi.org/10.1152/japplphysiol.00024.2003
Dokladny K, Lobb R, Wharton W et al (2010) LPS-induced cytokine levels are repressed by elevated expression of HSP70 in rats: possible role of NF-κB. Cell Stress Chaperones. https://doi.org/10.1007/s12192-009-0129-6
Dokladny K, Moseley PL, Ma TY (2006a) Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability. Am J Physiol Liver Physiol. https://doi.org/10.1152/ajpgi.00401.2005
Dokladny K, Wharton W, Lobb R et al (2006b) Induction of physiological thermotolerance in MDCK monolayers: contribution of heat shock protein 70. Cell Stress Chaperones. https://doi.org/10.1379/CSC-194R.1
Fox RH, Goldsmith R, Hampton IF, Hunt TJ (2017) Heat acclimatization by controlled hyperthermia in hot-dry and hot-wet climates. J Appl Physiol. https://doi.org/10.1152/jappl.1967.22.1.39
Garrett AT, Goosens NG, Rehrer NG et al (2009) Induction and decay of short-term heat acclimation. Eur J Appl Physiol. https://doi.org/10.1007/s00421-009-1182-7
Garrett AT, Rehrer NJ, Patterson MJ (2011) Induction and decay of short-term heat acclimation in moderately and highly trained athletes. Sport, Med
Gibson OR, Mee JA, Taylor L et al (2015a) Isothermic and fixed-intensity heat acclimation methods elicit equal increases in Hsp72 mRNA. Scand J Med Sci Sports 25:259–268. https://doi.org/10.1111/sms.12430
Gibson OR, Turner G, Tuttle JA, Taylor L, Watt PW, Maxwell NS (2015b) Heat acclimation attenuates physiological strain and the HSP72, but not HSP90α, mRNA response to acute normobaric hypoxia. J Appl Physiol 119:889–899. https://doi.org/10.1152/japplphysiol.00332.2015
Gómez AV, Galleguillos D, Maass JC et al (2008) CoREST represses the heat shock response mediated by HSF1. Mol Cell. https://doi.org/10.1016/j.molcel.2008.06.015
Higgins JPT, Altman DG, Gøtzsche PC et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. https://doi.org/10.1136/bmj.d5928
Hom LL, Lee ECH, Apicella JM, Wallace SD, Emmanuel H, Klau JF, Poh PY, Marzano S, Armstrong LE, Casa DJ, Maresh CM (2012) Eleven days of moderate exercise and heat exposure induces acclimation without significant HSP70 and apoptosis responses of lymphocytes in college-aged males. Cell Stress Chaperones 17:29–39. https://doi.org/10.1007/s12192-011-0283-5
Houmard JA, Costill DL, Davis JA et al (1990) The influence of exercise intensity on heat acclimation in trained subjects. Med Sci Sports Exerc. https://doi.org/10.1249/00005768-199010000-00012
Koishi M, Hosokawa N, Sato M et al (1992) Quercetin, an inhibitor of heat shock protein synthesis, inhibits the acquisition of thermotolerance in a human colon carcinoma cell line. Japanese J Cancer Res. https://doi.org/10.1111/j.1349-7006.1992.tb02748.x
Kuennen M, Dokladny K, Moseley P et al (2011) Thermotolerance and heat acclimation may share a common mechanism in humans. Am J Physiol Integr Comp Physiol. https://doi.org/10.1152/ajpregu.00039.2011
Laszlo A (1988) The relationship of heat-shock proteins, thermotolerance, and protein synthesis. Exp Cell Res. https://doi.org/10.1016/0014-4827(88)90409-0
Lee BJ, Mackenzie RWA, Cox V et al (2015) Human monocyte heat shock protein 72 responses to acute hypoxic exercise after 3 days of exercise heat acclimation. Biomed Res Int 2015:1–15. https://doi.org/10.1155/2015/849809
Lee BJ, Miller A, James RS, Thake CD (2016) Cross acclimation between heat and hypoxia: heat acclimation improves cellular tolerance and exercise performance in acute normobaric hypoxia. Front Physiol 7:1–15. https://doi.org/10.3389/fphys.2016.00078
Lee WC, Wen HC, Chang CP et al (2006) Heat shock protein 72 overexpression protects against hyperthermia, circulatory shock, and cerebral ischemia during heatstroke. J Appl Physiol. https://doi.org/10.1152/japplphysiol.01433.2005
Leon LR, Bouchama A (2015) Heat stroke. Compr Physiol. https://doi.org/10.1002/cphy.c140017
Li GC (1985) Elevated levels of 70,000 Dalton heat shock protein in transiently thermotolerant Chinese hamster fibroblasts and in their stable heat resistant variants. Int J Radiat Oncol Biol Phys. https://doi.org/10.1016/0360-3016(85)90376-1
Lorenzo S, Halliwill JR, Sawka MN, Minson CT (2010) Heat acclimation improves exercise performance. J Appl Physiol. https://doi.org/10.1152/japplphysiol.00495.2010
Lorenzo S, Minson CT (2010) Heat acclimation improves cutaneous vascular function and sweating in trained cyclists. J Appl Physiol. https://doi.org/10.1152/japplphysiol.00725.2010
Magalhães FDC, Amorim FT, Passos RLF et al (2010) Heat and exercise acclimation increases intracellular levels of Hsp72 and inhibits exercise-induced increase in intracellular and plasma Hsp72 in humans. Cell Stress Chaperones 15:885–895. https://doi.org/10.1007/s12192-010-0197-7
Malago JJ, Koninkx JFJG, Van Dijk JE (2002) The heat shock response and cytoprotection of the intestinal epithelium. Cell Stress Chaperones
Maloyan A, Horowitz M (2002) β-Adrenergic signaling and thyroid hormones affect HSP72 expression during heat acclimation. J Appl Physiol. https://doi.org/10.1152/japplphysiol.01122.2001
Maloyan A, Palmon A, Horowitz M (1999) Heat acclimation increases the basal HSP72 level and alters its production dynamics during heat stress. Am J Physiol Integr Comp Physiol. https://doi.org/10.1152/ajpregu.1999.276.5.r1506
Marshall HC, Campbell SA, Roberts CW, Nimmo MA (2007) Human physiological and heat shock protein 72 adaptations during the initial phase of humid-heat acclimation. J Therm Biol 32:341–348. https://doi.org/10.1016/j.jtherbio.2007.04.003
McClung JP, Hasday JD, He J et al (2007) Exercise-heat acclimation in humans alters baseline levels and ex vivo heat inducibility of HSP72 and HSP90 in peripheral blood mononuclear cells. Am J Physiol Integr Comp Physiol 294:R185–R191. https://doi.org/10.1152/ajpregu.00532.2007
Metcalfe A, Rosenthal R (2006) Meta-analytic procedures for social research. Stat. https://doi.org/10.2307/2348600
Morimoto RI (1998) Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev
Morton JP, MacLaren DPM, Cable NT et al (2006) Time course and differential responses of the major heat shock protein families in human skeletal muscle following acute nondamaging treadmill exercise. J Appl Physiol. https://doi.org/10.1152/japplphysiol.00046.2006
Murakoshi M, Sekine M (2012) [Measures by local government--actions to take in dealing with heat stroke for firefighters]. Nihon Rinsho
Nadel ER, Pandolf KB, Roberts MF, Stolwijk JA (2017) Mechanisms of thermal acclimation to exercise and heat. J Appl Physiol. https://doi.org/10.1152/jappl.1974.37.4.515
Nava RC, Zuhl MN, Moriarty TA et al (2019) The effect of acute glutamine supplementation on markers of inflammation and fatigue during consecutive days of simulated wildland firefighting. J Occup Environ Med. https://doi.org/10.1097/JOM.0000000000001507
Nielsen B, Hales JR, Strange S et al (1993) Human circulatory and thermoregulatory adaptations with heat acclimation and exercise in a hot, dry environment. J Physiol. https://doi.org/10.1113/jphysiol.1993.sp019482
Papamichael K, Tiligada E (2008) Heat shock proteins in adaptive and protective physiology and pathophysiology of the gastrointestinal mucosa. In: Heat shock proteins: new research
Parsell DA, Lindquist S (1993) The function of heat-shock proteins in stress tolerance: degradation and reactivation of damaged proteins. Annu Rev Genet 27:437–496. https://doi.org/10.1146/annurev.ge.27.120193.002253
Périard JD, Racinais S, Sawka MN (2015) Adaptations and mechanisms of human heat acclimation: applications for competitive athletes and sports. Scand. J. Med. Sci, Sport
Robinson S, Turrell ES, Belding HS, Horvath SM (1943) Rapid acclimatization to work in hot climates. Am J Phys 140:168–176. https://doi.org/10.1152/ajplegacy.1943.140.2.168
Rowell LB, Kraning KK, Kennedy JW, Evans TO (2017) Central circulatory responses to work in dry heat before and after acclimatization. J Appl Physiol. https://doi.org/10.1152/jappl.1967.22.3.509
Sandström ME, Siegler JC, Lovell RJ et al (2008) The effect of 15 consecutive days of heat-exercise acclimation on heat shock protein 70. Cell Stress Chaperones. https://doi.org/10.1007/s12192-008-0022-8
Sareh H, Tulapurkar ME, Shah NG, Singh IS, Hasday JD (2011) Response of mice to continuous 5-day passive hyperthermia resembles human heat acclimation. Cell Stress Chaperones 16:297–307. https://doi.org/10.1007/s12192-010-0240-8
Sawka MN, Leon LR, Montain SJ, Sonna LA (2011) Integrated physiological mechanisms of exercise performance, adaptation, and maladaptation to heat stress. Compr Physiol. https://doi.org/10.1002/cphy.c100082
Shi Y, Mosser DD, Morimoto RI (1998) Molecular chaperones as HSF1-specific transcriptional repressors. Genes Dev. https://doi.org/10.1101/gad.12.5.654
Shin YO, Oh JK, Sohn HS et al (2004) Expression of exercise-induced HSP70 in long-distance runner’s leukocytes. Journal of Thermal Biology, In
Taylor NAS (2014) Human heat adaptation. Compr Physiol. https://doi.org/10.1002/cphy.c130022
Tupling AR, Bombardier E, Stewart RD et al (2007) Muscle fiber type-specific response of Hsp70 expression in human quadriceps following acute isometric exercise. J Appl Physiol. https://doi.org/10.1152/japplphysiol.00771.2007
van Rhee H, Suurmond R, Hak T (2018) User manual for meta-essentials: workbooks for meta-analysis. SSRN Electron J. https://doi.org/10.2139/ssrn.3241355
Watkins AM, Cheek DJ, Harvey AE, Blair KE, Mitchell JB (2008) Heat acclimation and HSP-72 expression in exercising humans. Int J Sports Med 29:269–276. https://doi.org/10.1055/s-2007-965331
Xiao C, Wu T, Ren A et al (2003) Basal and inducible levels of Hsp70 in patients with acute heat illness induced during training. Cell Stress Chaperones. https://doi.org/10.1379/1466-1268(2003)8<86:BAILOH>2.0.CO;2
Yamada PM, Amorim FT, Moseley P, Robergs R, Schneider SM (2007) Effect of heat acclimation on heat shock protein 72 and interleukin-10 in humans. J Appl Physiol 103:1196–1204. https://doi.org/10.1152/japplphysiol.00242.2007
Zou J, Guo Y, Guettouche T et al (1998) Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell. https://doi.org/10.1016/S0092-8674(00)81588-3
Zuhl M, Dokladny K, Mermier C, Schneider S, Salgado R, Moseley P (2015) The effects of acute oral glutamine supplementation on exercise-induced gastrointestinal permeability and heat shock protein expression in peripheral blood mononuclear cells. Cell Stress Chaperones 20:85–93. https://doi.org/10.1007/s12192-014-0528-1
Zuhl M, Schneider S, Lanphere K et al (2014) Exercise regulation of intestinal tight junction proteins. Br J Sports Med
Zuhl MN, Lanphere KR, Kravitz L et al (2013) Effects of oral glutamine supplementation on exercise-induced gastrointestinal permeability and tight junction protein expression. J Appl Physiol. https://doi.org/10.1152/japplphysiol.00646.2013
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Nava, R., Zuhl, M.N. Heat acclimation-induced intracellular HSP70 in humans: a meta-analysis. Cell Stress and Chaperones 25, 35–45 (2020). https://doi.org/10.1007/s12192-019-01059-y
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DOI: https://doi.org/10.1007/s12192-019-01059-y