HEAT SHOCK PROTEIN GENE EXPRESSION IN RESPONSE TO STRESS AND AGING

众所周知，热和各种其他有害因素会导致 一组被称为热休克的高度保守蛋白质的表达 蛋白质(HSPs)。这些蛋白质似乎对细胞 动态平衡，已经在培养细胞中进行了广泛的研究，但 关于它们在体内的表达情况，人们知之甚少。In-This 我们正在研究热休克蛋白在啮齿类动物中的表达 体内的生理应激。特别关注热休克反应 在衰老过程中。以前，我们证明了HSP70的表达在 老年大鼠成纤维细胞的培养相对年轻大鼠成纤维细胞。我们 也证明了HSP70在老年动物中的表达减少， 在体内受到热应激，但反应减弱似乎 在温度调节方面的变化是次要的。在过去的一年里，我们有 在小鼠中，热休克蛋白70的表达也被诱导在棕色脂肪(主要是 产热器官)对冷应激作出反应。再一次，与年龄相关的 这一表达的下降是明显的，似乎是由于 至少在一定程度上，改变了温度调节。最近，我们观察到 在大鼠中，HSP70也是在束缚应激反应中诱导的。二 这种反应的重要特征是，归纳是相对 特异于肾上腺，涉及一种选择性的表达 特定的基因转录本。这些发现以及我们之前的 热休克蛋白70在脑区特异性定位表达的观察 与神经内分泌轴相关提示这与 细胞对压力的反应和经典的荷尔蒙应激反应。

Heat and a variety of other damaging agents are known to induce the expression of a set of highly conserved proteins known as the heat shock proteins (HSPs). These proteins, which appear to be critical for cellular homeostasis, have been studied extensively in cultured cells, but relatively little is known concerning their expression in vivo. In-this project we are examining the expression of HSPs in rodents in response to physiological stresses in vivo. Particularly focusing on the HSP response in aging. Previously, we demonstrated that HSP70 expression was impaired in cultured fibroblasts from aged rats relative to those of young rats. We also demonstrated that HSP70 expression was reduced in aged animals, subjected to heat stress in vivo, but the diminished response appeared to be secondary to alterations in thermoregulation. over the past year we have shown that in mice HSP70 expression is also induced in brown fat (the major heat generating organ) in response to cold stress. Again, an age-related decline in the expression is apparent and appears to be the result of at least in part, altered thermoregulation. More recently, we have observed that HSP70 is also induced in response to restraint stress in rats. Two important features of this response are that the induction is relatively specific to the adrenal gland and involves the selective expression of one particular gene transcript. These findings along with our previous observations of specific localized HSP70 expression in regions of the brain associated with the neuroendocrine axis suggest a link between this cellular response to stress and the classical hormonal stress response.