Fawcett T W, Xu Q, Holbrook N J
Section on Gene Expression and Aging, National Institute on Aging, Baltimore, MD 21224, USA.
Cell Stress Chaperones. 1997 Jun;2(2):104-9. doi: 10.1379/1466-1268(1997)002<0104:pohsih>2.3.co;2.
Studies in cultured cells have demonstrated that non-steroidal anti-inflammatory agents can potentiate heat-induced hsp70 expression through activation of HSF1 to a DNA binding state. We investigated the influence of aspirin on hsp70 expression in intact rats subjected to heat stress. Rats were injected intraperitoneally either with aspirin (100 mg/kg) or vehicle alone, 60 min prior to their placement at 37 degrees C or room temperature for 30 min. hsp70 mRNA expression was analyzed in lung, liver and kidney isolated from animals assigned to one of four different treatment paradigms; untreated controls, heat, aspirin, and aspirin-plus-heat. Comparison of hsp70 expression in the treatment groups revealed that in all tissues examined, aspirin-plus-heat treatment resulted in 3-4 fold higher levels of hsp70 mRNA relative to those seen with heat treatment alone. Little or no hsp70 mRNA expression was detected in the unheated groups, regardless of aspirin treatment. In keeping with the mRNA expression, Hsp70 protein levels were also elevated in aspirin-plus-heat treated animals. Aspirin treatment did not alter hsp70 protein expression in the absence of heat. In contrast to in vitro observations, aspirin treatment in vivo did not alter HSF1 DNA binding properties. Core body temperature measurements revealed that aspirin pretreatment enhanced the rise in body temperature seen in response to heat treatment. This increased hyperthermic response to heat stress probably accounts for the potentiation of hsp70 expression observed in aspirin-plus-heat treated rats. Given the widespread use of aspirin in humans within a dose range comparable to that used here, our findings are likely to have important physiological consequences.
在培养细胞中的研究表明，非甾体抗炎药可通过将热休克因子1（HSF1）激活至DNA结合状态来增强热诱导的hsp70表达。我们研究了阿司匹林对热应激完整大鼠中hsp70表达的影响。在将大鼠置于37℃或室温30分钟前60分钟，分别腹腔注射阿司匹林（100mg/kg）或单独注射赋形剂。对从分配到四种不同处理模式之一的动物分离的肺、肝和肾中的hsp70 mRNA表达进行了分析；未处理的对照、热应激、阿司匹林处理以及阿司匹林加 热应激处理。各处理组中hsp70表达的比较显示，在所有检测的组织中，与单独热应激处理相比，阿司匹林加 热应激处理使hsp70 mRNA水平升高了3至4倍。无论是否进行阿司匹林处理，在未加热的组中几乎检测不到或未检测到hsp70 mRNA表达。与mRNA表达一致，在阿司匹林加 热应激处理的动物中Hsp70蛋白水平也升高。在无热应激的情况下，阿司匹林处理不会改变hsp70蛋白表达。与体外观察结果相反，体内阿司匹林处理不会改变HSF1的DNA结合特性。核心体温测量显示，阿司匹林预处理增强了热应激处理后体温的升高。这种对热应激的热反应增强可能解释了在阿司匹林加 热应激处理的大鼠中观察到的hsp70表达增强现象。鉴于阿司匹林在人类中的广泛使用剂量范围与此处所用剂量相当，我们的发现可能具有重要的生理意义。
