Study of Dominant-positive Heat Shock Factor 1 on 6-OHDA-induced Cell Death / 中国生物工程杂志

ABSTRACT

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.