Protective Effect Of Estrogen Against Serum Deprivation Induced Apoptosis In PC12 Cells Stably Transfected With Estrogen Receptor Alpha

The congnitive dysfunction in patients with Alzheimer's disease(AD) corelates with apoptosis in some specific regions in the brain. This apoptosis is considered to be caused by several factors, such as genomic susceptibility, lack of neurotrophic factors, abnormal aniyloid protein, mitochondrial abnormality, oxidative stress, etc. Recently, increasing number of evidence have indicated that estrogen has trophic and protective effects in the nervous system and can dramatically decrease the morbidity of Alzheimer's disease. In this study we used a rat adrenal pheocbromocytoma cell line, PC12 to investigate the effect of expressing estrogen receptor alpha in PC12 on the apoptosis induced by serum deprivation. PC12 cells were transfected with expressing vector containing full-length human estrogen receptor alpha (hER α) eDNA using standard calcium phosphate method and the positive tranfectants (PC12ER) that express hER a were obtained. Cells transfected with vector DNA alone were used as control cells. The results from cytoflowmetry and MTT assay indicated that estrogen treatment can promote the growth in normal culture and significantly decrease the apoptotic rates in PC12ER cells after the serum deprivation. These effects are dose and time- dependent in certain range of dose and time. Moreover, the decrease in apoptotic rate is not due to the propagation of survival cells, but due to the alleviation of apoptosis. Meanwhile, in the control cells, estrogen had no such effect. Tamoxifen, a partial antagonist for estrogen receptor, fails to block estrogen's protective effect. Our findings demonstrate that estrogen can receptor-dependently prevent PC12 cells from apoptosis induced by serum deprivation. These also provide experimental foundation for the use of estrogen replacement therapy (ERT) in AD patients.