Wiegant F A, Spieker N, van Wijk R
Department of Molecular Cell Biology, Utrecht University, The Netherlands.
Toxicology. 1998 May 15;127(1-3):107-19. doi: 10.1016/s0300-483x(98)00035-3.
In this paper, the pattern of induction of heat shock proteins (hsps) was studied in cultured Reuber H35 rat hepatoma cells by sequential application of different stressors. We analyzed whether a specific stress condition is able to induce an enhanced sensitivity to a subsequent application of a low dose of either the same or another stressor (self-sensitization and cross-sensitization, respectively). As a measure of sensitization, the stimulation of hsp induction was employed. Three different stressor conditions (heat shock, sodium arsenite and cadmium chloride) were used in doses which exerted a similar impact on overall protein synthesis. A synergistic effect in induction of the synthesis of various hsps was observed when a high stressor dose was followed by an 8-h incubation in a lower stressor dose in both self- and cross-sensitization experiments. The low-dose conditions used as second treatments did not induce any responses in non-pretreated cells. Studies in cultured cells have demonstrated stressor-specific hsp induction patterns. In this study we analyzed whether the pattern of hsps induced by the low-dose condition is characteristic for the first sensitizing stressor or for the secondary stressor applied in a low dose. The pattern of hsps which was induced above the level of the high-dose effect, due to the incubation with the secondary applied low-dose condition, was found to be characteristic for the secondary stressor and not for the sensitizing primary treatment. These results are of importance for an improved understanding of the regulation of heat shock protein synthesis in conditions of self- and cross-sensitization, as well as for a proper use of hsps as biomarkers of exposure to environmental stress.
在本文中，通过依次施加不同应激源，研究了培养的鲁伯H35大鼠肝癌细胞中热休克蛋白（hsps）的诱导模式。我们分析了特定应激条件是否能够诱导对随后施加的低剂量相同或另一种应激源的敏感性增强（分别为自身致敏和交叉致敏）。作为致敏的一种衡量方法，采用了对hsp诱导的刺激。使用了三种不同的应激源条件（热休克、亚砷酸钠和氯化镉），其剂量对总体蛋白质合成产生相似的影响。在自身致敏和交叉致敏实验中，当高剂量应激源之后接着在低剂量应激源中孵育8小时时，观察到各种hsps合成诱导中的协同效应。用作第二次处理的低剂量条件在未预处理的细胞中未诱导任何反应。在培养细胞中的研究已经证明了应激源特异性的hsp诱导模式。在本研究中，我们分析了低剂量条件诱导的hsps模式是对第一次致敏应激源还是对以低剂量施加的第二次应激源具有特征性。由于与第二次施加的低剂量条件孵育，在高剂量效应水平之上诱导的hsps模式被发现对第二次应激源具有特征性，而对致敏的初次处理则不具有特征性。这些结果对于更好地理解自身致敏和交叉致敏条件下热休克蛋白合成的调节以及正确使用hsps作为环境应激暴露的生物标志物具有重要意义。
