Pathophysiological mechanism through the regulation of the transcriptional factor, c-fos, gene expression.

1)应激诱导的c-fos基因和AP-1活性的升高虽然人们普遍认为c-fos基因的上游不含有热休克元件(HSE)，但我们在人、大鼠和小鼠的基因中发现了HSE的共同序列(BBRC254：566,1999)。由于rostaglandin A1(PGA1)增加了热休克元件(HSE)介导的转录，从而增强了包括热休克蛋白在内的HSE相关基因的表达，我们推测PGA1可能通过HSE增加c-fos的表达。随后的研究表明，c-fos的表达至少部分是通过增加热休克因子-1与HSE的结合，以及PGA1增强激活蛋白-1(AP-1)的活性。有趣的是，只要在介质中存在PGA1，标准的荧光素酶报告基因检测就不能检测到由PGA1促进的AP-1介导的转录。相反，可以通过检查lu…来检测它在PGA1存在的情况下，或在去除PGA1后立即测量荧光素酶活性，可获得更高的ciferase mRNA水平。这些结果表明，一些应激反应基因的蛋白产物可以增加，不是在应激条件下，而是在应激恢复后立即增加(MCE 164：77,2000)2)环境激素样物质的检测在HSE的研究过程中，我们一直对雌激素活性感兴趣，因为它可以促进c-fos基因和热休克蛋白的表达。由于我们经常在对照培养皿中检测荧光素酶时遇到麻烦，我们怀疑培养皿中是否存在具有雌激素活性的激素样物质。我们的实验显示，许多类型的聚苯乙烯碟子释放雌激素杂质，这一特性在使用雌激素反应细胞进行研究或研究这种激素及其类似物的细胞效应时应该考虑到(自然生物技术19：812,2001)。较少

1) Elevation of c-fos gene and AP-1 activity induced by stressesAlthough it has been widely accepted that the c-fos gene, which is responsive to various stresses, does not harbor the heat shock element (HSE) in its upstream region, we found the consensus-sequence for the HSE in the human, rat and mouse genes (BBRC 254:566, 1999). Since rostaglandin A1 (PGA1) increases heat shock element (HSE)-mediated transcription, thereby enhancing expression of HSE-bearing genes, including heat shock proteins, we hypothesized that PGA1 might increase c-fos expression through the HSE. Following investigation has revealed that c-fos expression at least partly by increasing the binding between heat shock factor-1 and the HSE, and that PGA1 enhances activity of activating protein-1 (AP-1). Interestingly, so far as PGA1 is present in the medium, AP-1-mediated transcription enhanced by PGA1 cannot be detected by the standard luciferase reporter gene assay. Instead, it can be detected by either checking lu … More ciferase mRNA levels in the presence of PGA1 or measuring luciferase activities just after removal of PGA1. These results shows that protein products of some stress-responsive genes can increase, not during the stressful condition, but immediately after recovery from stress(MCE 164:77, 2000).2) Detection of environmental hormone-like substancesIn the process of the studies on HSE, we have been interested in estrogenic activity because it can enhance expression of c-fos gene as well as heat shock proteins. Since we often experienced troubles with the assay for luciferase in control dishes, we got suspicious of the existence of hormone-like substances with estrogenic activity released from the culture dishes. Our experiments reveals that many types of polystyrene dishes release estrogenic impurities, a property that should be taken into account when carrying out research using estrogen-responsive cells or studying the cellular effects of this hormone and its analogs (Nature Biotechnology 19:812, 2001). Less