Heat shock proteins and the heat shock response during hyperthermia and its modulation by altered physiological conditions.

The fundamental functions of heat shock proteins (HSPs) are molecular chaperoning and cellular repair. There is little literature on the association between the numerous functions of HSPs and systemic integrative responses, particularly those controlled by the central nervous system. This chapter focuses on the role played by members of the HSP70 superfamily, universally recognized as cytoprotectants during heat stress, within the physiological context of hyperthermia and with its superimposition on situations of chronic stress. In the nucleus tractus solitarius, HSP70 levels enhance the sensitivity of sympathetic and parasympathetic arms of the autonomic nervous system to attenuate heat stroke-induced cerebral ischemia and hypotension. Chronic stressors that alter the heat shock response may affect the physiological profile during hyperthermic conditions. Upon aging, significantly lower HSP70 production is noted in the ventral paraventricular and lateral magnocellular nuclei. Likewise, results from cultured cells suggest that the age-related decline in HSP70 expression is constitutive and is due to decreased binding of the heat shock factor 1 (HSF-1) to the heat shock element (HSE) and diminished HSP70 transcription. These changes may be associated with decreased thermotolerance upon aging, although HSP70 production in response to other stressors is not affected. Heat acclimation (AC), in contrast, increases tissue reserves of HSP70 and accelerates the heat shock response. AC protects epithelial integrity, vascular reactivity and interactions with cellular signaling networks, enhancing protection and delaying thermal injury. The link between HSP70 and the immune system is discussed with respect to exercise. Exercise enhances the immune response via production of HSP72 in central and peripheral structures. At least in part, the effects of HSP72 in the brain are mediated via eHSP72-circulating HSPs providing a "danger signal" to activate the immune response. In summary, HSPs are primarily cytoprotective components, the physiological situations described in this chapter infer their pivotal role in central control of integrative systems.