Oestrogen prevention of neural cell death correlates with decreased expression of mRNA for the pro-apoptotic protein Nip-2

We have recently identified nip-2 as a gene target for 17 beta-oestradiol a ctivity in the neuroblastoma SK-ER3 cells expressing the oestrogen receptor (ER) alpha. Here we show 17 beta-oestradiol treatment of neuroblastoma and rat embryo neurones in culture blocks the increase in nip-2 mRNA induced b y apoptotic stimuli and prevents cell death as indicated by cell counting, 3,(4,5-dimethylthiazol-2-yl)2,5-diphenil-tetrazoliumbromide and DNA fragmen tation assays. Neither of these effects are observed in the presence of the specific ER antagonist ICI 182,780, and are absent in neuroblastoma cells not expressing ER. We propose that nip-2 plays a relevant role in neural ce ll apoptosis and that a decrease in its expression is instrumental for the oestrogen anti-apoptotic effect described here. The experimental evidence p resented supports the recent hypothesis of a protective role of oestrogens in neurodegenerative diseases such as Alzheimer's disease and highlights th e importance of the development of new ER ligands for the prevention of neu ral cell damage.