中文摘要：

热休克因子1是真核细胞应激反应时热休克蛋白表达的主要转录调控因子。它在非应激条件下被抑制性复合体抑制以非活化形式存在,只有在受到应激时才会暂时活化。通过基因突变得到的正显性突变体在不需要外界环境刺激的条件下就能激活细胞内源性热休克蛋白的表达。环境神经毒素是引起帕金森病的一个重要因素,它们能够氧化损伤多巴胺能神经元,最终引起细胞死亡。Western blot和双荧光素酶检测证明,在SH-SY5Y细胞中转染正显性热休克因子1突变体能够明显上调HSP70的表达。并且通过检测细胞培养基中的乳酸脱氢酶的含量证明正显性热休克因子1突变体能够显著抑制神经毒素6-羟基多巴胺诱导的细胞死亡。这些结果表明,正显性热休克因子1突变体在帕金森病的防治方面可能具有潜在的应用前景。

英文摘要：

In eukaryotic cells,heat shock factor 1 is the main specific transcription factor mediating the enhanced expression of heat shock proteins when cells experience stresses.It is kept in a latent state by inhibitory complexes under unstressed conditions.It is only transiently activated in response to diverse forms stresses.Dominant-positive heat shock factor 1 has been developed through deletion-mutation.It can activate the expression of endogenous heat shock proteins in the absence of stresses.Environmental neurotoxins play an important role in the pathogenesis of Parkinson＇s disease.The neurotoxins induce cell death of dopamine neurons through oxidative damage.The results of Western blot and dual-luciferase analysis indicate that the expression of HSP70 was greatly up-regulated in dopaminergic SH-SY5Y cells transfected with dominant-positive heat shock factor 1.To investigate the effect of dominant-positive heat shock factor 1 on 6-OHDA-induced apoptosis in dopaminergic SH-SY5Y cells,the release of lactate dehydrogenase was detected.The result argues that dominant-positive heat shock factor 1 significantly inhibits neurotoxin 6-OHDA-induced cell death in SH-SY5Y cells.The cyto-protective role may be attributed to HSP70 activated by dominant-positive heat shock factor 1.Taken together,it is possible that dominant-positive heat shock factor 1 can be used to prevent or cure Parkinson＇s disease.