HEAT SHOCK IN TOXICITY ASSAYS

热休克蛋白（HSP）或应激蛋白基因的表达是 通过一系列不同的化学物质和治疗方法， 到细胞。 通常，用诱导hsp的试剂预处理 合成使细胞抵抗随后的挑战， 或其他可能导致死亡的物质 的 基因是普遍存在的，并编码少量相对较高的 保守蛋白 已知几种hsp与其他蛋白质结合， 其中一些（包括70，000道尔顿或hsp 70蛋白）具有 优选未折叠的多肽，并作为分子 分子伴侣，促进重要的细胞过程，如蛋白质 合成和贩运。 热休克蛋白基因的转录调控是 由hsp基因特异性转录因子HSF介导， 似乎受未结合的HSP 70的浓度调节。 因为 在它们的调节中，热休克蛋白被认为是可能的分子- 毒性的生物标志物。 根据它们的性质， 假设hsps，特别是hsp 70类，也可能 与许多生物的分子作用机制有着错综复杂的关系， 有毒物质 这个建议是为了描述，使用鼠标 肝毒性模型，hsp基因表达对暴露的反应， 生物体的良好特性的毒物，并测试的假设， 热休克蛋白保护肝细胞免受许多毒物的损伤， 通过相互作用参与许多毒物的作用机制， 直接或间接地，与由这些产生的加合蛋白质 有毒物质生物转化后，和热休克蛋白基因上调 表达反映了细胞对有毒物质的反应， 额外的热休克蛋白“中和”加合蛋白。

Expression of heat shock protein (hsp) or stress protein genes is enhanced by a diverse set of chemicals and treatments that are stressful to cells. Frequently, pretreatment with an agent that induces hsp synthesis renders cells resistant to subsequent challenges with the same or other agents under conditions that would otherwise cause death. The genes are ubiquitous and encode a small number of relatively highly conserved proteins. Several hsps are known to bind to other proteins, some of them (including the 70,000 dalton or hsp70 proteins) having a preference for unfolded polypeptides, and to function as molecular chaperones, facilitating important cellular processes such as protein synthesis and trafficking. Regulation of transcription of hsp genes is mediated by hsp gene-specific transcription factor HSF whose activity appears to be regulated by the concentration of unengaged hsp70. Because of their regulation, hsps are being discussed as possible molecular- biological markers for toxicity. Based on their properties we hypothesize that hsps, especially those of the hsp70 class, may also be intricately related to the molecular mechanisms of action of many toxicants. This proposal is to characterize, using a mouse hepatotoxicity model, hsp gene expression in response to exposure of the organism to well-characterized toxicants, and to test the hypotheses that hsps protect hepatic cells from damage by many toxicants, that they may participate in the mechanisms of action of many toxicants by interacting, directly or indirectly, with adducted proteins produced by these toxicants following bioconversion, and that upregulation of hsp gene expression reflects the cell's response to toxicants, serving to provide extra hsps to "neutralize" adducted proteins.