Extracellular and cellular Hsp72 differ as biomarkers in acute exercise/environmental stress and recovery

Abstract

Stress-inducible Hsp72 is a potential biomarker to track risk of exertional heat illness during exercise/environmental stress. Characterization of extracellular (eHsp72) vs cellular Hsp72 (iHsp72) responses is required to define the appropriate use of Hsp72 as a reliable biomarker. In each of four repeat visits, participants (n = 6 men, 4 trials; total n = 24): (a) passively dehydrated overnight, (b) exercised (2 h) with no fluid in a hot, humid environmental chamber, (c) rested and rehydrated (1 h), (d) maximally exercised for 0.5 h, and (e) returned after 24 h of at-home recovery and rehydration. We measured rectal temperature, hydration status (% body mass loss, urine markers, serum osmolality), and Hsp72 (ELISA, flow cytometry. eHsp72 (circulating) and iHsp72 (CD3 PBMCs) correlated (P < 0.05) with markers of heat, exercise, and dehydration stresses. eHsp72 immediately post-exercise (>15% above baseline, P < 0.05) decreased back to baseline levels by 1 h post-exercise, but iHsp72 expression continued to rise and remained elevated 24 h post-exercise (~2.5-fold baseline, P < 0.05). These data suggest that in addition to the classic physiological biomarkers of exercise heat stress, using cellular Hsp72 as an indicator of lasting effects of stress into recovery may be most appropriate for determining long-term effects of stress on risk for exertional heat illness.

The Hsp72 and Hsp90α mRNA Responses to Hot Downhill Running Are Reduced Following a Prior Bout of Hot Downhill Running, and Occur Concurrently within Leukocytes and the Vastus Lateralis

“…HSP72 protein concentrations (due to translational inhibition) may not necessary directly represent the magnitude of the cellular stress response therefore the mRNA response has been proposed as more appropriate (Amorim et al, 2015; Gibson et al, 2015a; Lee et al, 2015). A reduction in the mRNA response is therefore representative of a gain in protein concentration (Marshall et al, 2007).…”

Hsp72 and Hsp90α mRNA transcription is characterised by large, sustained changes in core temperature during heat acclimation

“…The rate of rise in core temperature is also important to increase plasma concentrations (Périard et al 2012). More relevant to acquiring thermotolerance (Kregel 2002) is the change in iHSP72 and iHSP90α (Lee et al 2015). The accumulation of greater iHSP72 is more closely linked to the absolute (final) and change (delta) in core temperature (Magalhães et al 2010) during HA.…”

“…cytoprotective) HSP72 protein translation that is retained beyond the initial stressor (Marshall et al 2007;Périard et al 2015). Therefore, the usefulness of extracellular HSPs to characterise acquired thermotolerance (Moseley 1997;Kregel 2002), to identify cessation of the cellular stress response following adaptation in vivo (McClung et al 2008;Kuennen et al 2011) and ex vivo (McClung et al 2008), or to identify functional roles in disease states (Henstridge et al 2014a;Krause et al 2015a) is inferior to that of the HSP gene transcript or translated protein (Lee et al 2015). At present, the precise physiological signals for increasing Hsp72 mRNA and Hsp90α mRNA are unknown, as is whether these genes transcribe to similar stimuli and similar magnitudes during exercise/exercise-heat stress.…”

“…At present, the precise physiological signals for increasing Hsp72 mRNA and Hsp90α mRNA are unknown, as is whether these genes transcribe to similar stimuli and similar magnitudes during exercise/exercise-heat stress. Accordingly, similar characterisation of Hsp72 and Hsp90α gene transcription to that of eHSP72 is required given their direct relationship with thermotolerance (Lee et al 2015).…”

Effects of severe whole-body hyperthermia on ovarian hormone and extracellular Hsp72 responses in young adult women

“…To date, however, despite current knowledge of sex-specific mechanisms of human thermoregulation to heat stress [3][4][5]23,24], most thermal research has been conducted in men; thus, our general understanding of the eHsp72 and hormonal responses to severe WBH is based on data obtained from male subjects. Existing evidence indicates that circulating eHsp72 is highly stress-inducible and normally responds to hyperthermia, exercise, oxidative stress, osmotic stress, infection or inflammation, protein damage, and many other stimuli in a systemic, dose-dependent manner [25][26][27][28][29]. In response to heat stress, eHsp72 expression is upregulated via a specific exocytotic pathway by the neuroendocrine hormone epinephrine in humans [11], or by norepinephrine in animals [25].…”