HSP Responses

HSP Responses To Exercising In a Warm Environment

David Simar1, Patricia Ruell2, Corinne Caillaud2 1 School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney NSW 2052, Australia. 2 Faculty of Health Science, The University of Sydney, Cumberland Campus, P.O. Box 170, Lidcombe NSW 1825, Australia.

Heat Shock Proteins: definition and induction

Heat shock proteins (HSP) were initially described in salivary gland cells from drosophila that were exposed to heat stress (Ritossa, 1962). They represent a very conservative class of cytoprotective proteins specifically induced at the cellular level in response to several environmental stressors (heat shock, cellular energy depletion, oxidative stress or inflammation amongst other). 

Those proteins have been classified in different super families according to their apparent molecular weight, resulting in a classification including HSP of low molecular weight (between 8 and 32-kDa) and the 40k-Da, 60-kDa, 70-kDa, 90-kDa and the 100-kDa superfamilies as described in table 1 (for more information please refer to (Powers et al., 2008; Snoeckx et al., 2001).

Among these different super families, the inducible form of the 70-kDa family, i.e., Hsp72, has received the most attention probably due to its critical role in cytoprotection by preventing abnormal folding of newly synthesized polypeptides, or by assisting in the repair of damaged proteins or in the degradation of irreversibly damaged proteins.

However, the other families of HSP have started to attract more attention, especially during the last decade.

Super family Isoforms Localisation Function
Small HSPs Ubiquitin, Cytosol, nucleus Protein degradation,
Hsp10 mitochondria oxidative stress tolerance
Hsp20-30kDa   Hsp60 co-factor
Hsp40 Hsp40 Cytosol, nucleus Hsp72 co chaperone
Hsp47 endoplasmic reticulum Normal protein folding
Hsp60 Hsp60 Mitochondria Normal protein folding
Hsp70 Hsp72 Cytosol, nucleus Thermotolerance,
Hsc73 mitochondria Normal protein folding
mtHsp70   Protein transport to mitochondria
Hsp90 Hsp90 Cytoplasm Steroid hormone receptors interaction
Hsp100 Hsp104-110 Cytosol, nucleus Thermotolerance
ORP150 endoplasmic reticulum ischemic tolerance

Table 1. Heat shock proteins super families

Although the induction of HSP was initially described in response to heat exposure, several other factors have since been shown to activate the same cascade of events leading to HSP induction. Amongst those factors, hyperthermia, oxidative stress, inflammation, cellular damage (through calcium overload), hypoxia/ischemia and cellular energy depletion are the most commonly observed.

Interestingly, most of these factors have also been reported during or in response to exercise (Powers et al., 2001). Of interest as well is the observation that the intensity of the stimulus could directly modulate the level of induction and that the association of several factors could actually exert an additive effect on the HSP response to those stimuli.

In support to this, we (Ruell et al., 2004), and other (Kiang et al., 1998) have reported that Hsp72 induction during heat exposure was highly dependent on temperature levels.

The same observation was reported in response to different levels of muscle damage (Gjovaag et al., 2006) and oxidative stress (Calabrese et al., 2004).

Heat Shock Proteins and Exercise

Exercise represents a very interesting model to study HSP expression since it associates a wide range of factors involved in the induction of these proteins. Those factors can be observed on the model developed in Figure 1 (Snoeckx et al., 2001).

This model describes the signalling pathways activated in response to oxidative stress, hyperthermia, hypoxia, altered substrate availability, damage resulting from stretch and catecholamines, all of which have been reported during exercise.

As the intensity of those different factors has a direct impact on the level of HSP induction, it has then been hypothesised that, similarly, exercise intensity, duration and type could impact on the level of HSPs expression.

This has now been confirmed in different types of tissues and both in animals and human (Demirel et al., 1999; Fehrenbach et al., 2005; Gjovaag et al., 2006; Milne and Noble, 2002). This cumulated evidence support the fundamental role that the intensity, the duration and the type of exercise can play on the induction of HSP in response to exercise.

Figure 1: Performance obtained by 11-12 years acclimated children in a 31°C water during a 800-m front crawl swimming, with (SC) and without swim cap (WSC)

Of high interest as well, is the differential impact of acute and chronic exercise. We (Simar et al., 2007; Simar et al., 2004), and other (Fehrenbach and Niess, 1999; Khassaf et al., 2001; Morton et al., 2006) showed that a single boot of exercise results in a significant increase in HSP expression in human leukocytes and skeletal muscles.

Chronic exercise or training on the other way seems to down regulate the level of HSP expression since a lower expression of a wide range of HSP has been reported in leukocytes from active subjects when compared to their sedentary counterparts (Fehrenbach and Niess, 1999; Shastry et al., 2002; Simar et al., 2007).

The response to training in skeletal muscles seems to be less consistent (Gjovaag and Dahl, 2006; Gjovaag et al., 2006; Liu et al., 1999) but could be explained by a different pattern of expression in different fibre types (Liu et al., 2006). Further investigations seem to be needed to elucidate the role of training and training status on HSP expression in different tissues in human.

Exercise in the heat and Heat Shock Proteins expression

Both exercise and increased temperature have been reported to potentially induce HSP, however their additional impact on HSP expression is yet to be fully understood. The direct impact of heat exposure on HSP has lead to the first description of HSP induction (Ritossa, 1962) and has since then been extensively investigated (Horowitz and Robinson, 2007).

As we have previously described, both the duration and intensity of the hyperthermia can modulate the HSP response. During exercise, temperature has been hypothesised to play a significant role in the induction of HSP although conflicting results have been recently reported (Morton et al., 2007).

In this context, the response to exercise under high environmental temperature is still unclear. A single exposure to high temperature, obtained passively or in response to exercise did not elicit a significant HSP induction (Lovell et al., 2008; Watkins et al., 2007). However, chronic exposure was reported to increase resting expression of HSP (Yamada et al., 2007) but could also blunt the response to an additional heat stress (McClung et al., 2008).

Eventually it has recently been described that the HSP response after a long distance running event was tightly related to the level of heat exertion experienced by the runners (Ruell et al., 2006). This seems to suggest that elevated resting levels of HSP could represent a marker of thermotolerance, whereas the exact significance of abnormally high induction in response to exercise in warm environment still needs to be elucidated (Ruell et al., 2006; Yamada et al., 2007).

Heat Shock proteins response to exercising under warm environment is starting to attract more attention due to its critical role in thermotolerance. However, further investigations are required to clarify its exact role and significance in this context.


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