Horowitz Michal, Robinson Sharon D M
Laboratory of Environmental Physiology, Faculty of Dental Medicine, The Hebrew University, POB 12272, Jerusalem 91120, Israel.
Prog Brain Res. 2007;162:433-46. doi: 10.1016/S0079-6123(06)62021-9.
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.
热休克蛋白（HSPs）的基本功能是分子伴侣作用和细胞修复。关于HSPs众多功能与全身整合反应之间的关联，尤其是由中枢神经系统控制的反应，相关文献较少。本章重点关注HSP70超家族成员在热应激期间普遍被认为是细胞保护剂，在热疗的生理背景下以及其叠加在慢性应激情况下所起的作用。在孤束核中，HSP70水平可增强自主神经系统交感和副交感神经分支的敏感性，以减轻热射病诱导的脑缺血和低血压。改变热休克反应的慢性应激源可能会影响热疗条件下的生理特征。随着年龄增长，在室旁腹侧和外侧大细胞中观察到HSP70产生显著降低。同样，培养细胞的结果表明，HSP70表达随年龄下降是组成性的，并且是由于热休克因子1（HSF-1）与热休克元件（HSE）的结合减少以及HSP70转录减少所致。这些变化可能与衰老时耐热性降低有关，尽管HSP70对其他应激源的反应不受影响。相比之下，热适应（AC）可增加HSP70的组织储备并加速热休克反应。AC可保护上皮完整性、血管反应性以及与细胞信号网络的相互作用，增强保护并延迟热损伤。关于运动，讨论了HSP70与免疫系统之间的联系。运动通过在中枢和外周结构中产生HSP72来增强免疫反应。至少部分地，HSP72在大脑中的作用是通过循环HSPs提供“危险信号”来激活免疫反应介导的。总之，HSPs主要是细胞保护成分，本章所述的生理情况表明它们在整合系统的中枢控制中起关键作用。
