Whole-body hyperthermia-induced thermotolerance is associated with the induction of Heat Shock Protein 70 in mice

Abstract

SUMMARY Molecular mechanisms of whole-body thermotolerance (WBT) in mammals have not been investigated thoroughly. The purpose of this study was to assess the induction of the 70 kDa heat shock protein (HSP70) and antioxidant enzyme activity in animal WBT, which was induced by whole-body hyperthermia (WBH) in mice. As a preconditioning treatment, WBH was applied to mice to induce WBT. Synthesis of inducible HSP70 (HSP70i) and quantification of its increased level in liver were investigated by one- and two-dimensional polyacrylamide gel electrophoresis and immunoblotting. HSP70i synthesis in mice liver was induced by non-lethal WBH (41°C, 30 min). When compared to control animals, the level of liver HSP70i increased substantially (by 3.6-fold; P<0.0001). When exposed to 30 min of hyperthermia preconditioning, and after recovery for 48 h, the survival rate was 88.2 %, which was significantly higher than that of the control group (37.5 %; P<0.01). Moreover, the survival rate of animals subjected to preconditioning for 15 min was 72.2 %, which was also significantly higher than that of the control group (P<0.05). In contrast, the survival rate of animals subjected to preconditioning for 45 min was 63.5 %, which was not different from the control group. Nonetheless, the protection index of the group subjected to 15 min and 30 min of preconditioning was 1.93 and 2.37, respectively. Furthermore, to assess their contributions to WBT, the activities of antioxidant enzymes were also measured. After 48 h of recovery in preconditioned animals, hepatic antioxidant enzyme activities, including superoxide dismutase, catalase and glutathione peroxidase, had not changed significantly. To study the molecular mechanism of WBT, we successfully developed a mouse model and suggest that, rather than the activities of antioxidant enzymes, it is HSP70i that has a role to help animals survive during severe heat stress.

Augmentation of Thermotolerance in Primary Skin Fibroblasts from a Transgenic Pig Overexpressing the Porcine HSP70.2

“…We have previously showed that synthesis of HSP70 in liver induced by whole body hyperthermia is associated with the survival in mice and the survival rate (88.2%) of animals subjected to preconditioning markedly exceeded that of the control group (37.5%) (King et al, 2002). Because of failure to express detectable level of HSP70, we could not demonstrate the protein function in HSP70 transgenic mice driven by CMV promoter (the same construct used in this study).…”

“…A plenty of studies have documented thermotolerance in cultured cells and in animals other than mammals (Laszlo and Li, 1985;Mizzen and Welch, 1988;Ulmasov et al, 1992;Kampinga, 1993;Mosely, 1997;Theodorakis et al, 1999). Presently, few studies revealed that thermotolerance in mice can be induced by whole body hyperthermia (Kapp and Lord, 1983;Weshler et al, 1984;King et al, 2002). Moreover, the correlation between myocardial injury due to ischemia and the expression of inducible HSP70 under the control of β-actin promoter in transgenic mice has been reported (Marber et al, 1995;Hutter et al, 1996;Trost et al, 1998).…”

Effect of Acute Heat Stress on Heat Shock Protein 70 and Its Corresponding mRNA Expression in the Heart, Liver, and Kidney of Broilers

“…HSPs may play important roles in protein assembly and disassembly (Bukau et al, 2000;Hartl and Hayer-Hartl, 2002), protein folding and unfolding (Hartl, 1996;Mayer and Bukau, 2004;Zietkiewicz et al, 2004), protein translocation (Ryan and Pfanner, 2001), and the refolding of damaged proteins (Hightower, 1991;Glover and Lindquist, 1998;Maloyan et al, 1999). Of the many expressed HSPs, those with a molecular weight of approximately 70 kDa appear to be most closely associated with heat tolerance (Craig and Gross, 1991;Wang and Edens, 1998;King et al, 2002).…”

Heat shock protein and gene regulation in goats during heat stress

“…HSPs are released intra cellularly and extra cellularly in response to various environmental stresses (Sonna et al 2002, Hecker et al 2011) in inducible form and can be an indicator of stress in cells (Sonna et al 2002). The regulation of HSP production is critical to cell survival and among the HSPs, Hsp70 has a significant role in cell thermo-tolerance and animal survival (King et al 2002). Understanding the regulation of heat stress at cellular level and expression pattern of Hsp70 gene will throw light on the mechanism of heat stress adaptation in goats.…”