Effects of estrogen on AF64A-induced apoptosis in NG108-15 cells

In this study, we show that pretreatment with physiological concentrations (1–100 nM) of 17β-estradiol decreased apoptosis induced by ethylcholine aziridinium (AF64A), a choline toxin, in the cholinergic neuronal cell line NG108-15. These protective effects were observed after short-term (30 min) pretreatment, and were blocked by treatment with an estrogen receptor antagonist and inhibitors of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK). The protective effects were, however, not reversed by a protein synthesis inhibitor. Furthermore, we examined the effects of 17β-estradiol on choline uptake in NG108-15 cells. Although choline uptake was inhibited by a selective inhibitor of choline uptake, hemicholinium-3, it was not altered by treatment with 17β-estradiol. These results indicated that the protective effect of 17β-estradiol on AF64A-induced apoptosis could be nongenomic, and that this effect may be due to the activation of PI3K/Akt and/or MEK/extracellular signal-regulated kinase (ERK) pathways.