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 17beta-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 17beta-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 17beta-estradiol. These results indicated that the protective effect of 17beta-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.
Kuwagata
Yusuke
Y
Department of Electrical Engineering and Bioscience, Center for Advanced Biomedical Sciences, Waseda University, 2-2, Wakamatus-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
Inoue
Hiroko
H
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001388:Aziridines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D045744:Cell Line, Tumor; D002794:Choline / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity; D018678:Cholinergic Agents / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D006426:Hemicholinium 3 / Q000494:pharmacology; D006825:Hybridomas; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D009466:Neuromuscular Blocking Agents / Q000037:antagonists & inhibitors / Q000633:toxicity; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000109:Acetylcholine; D001388:Aziridines; D002794:Choline; D018678:Cholinergic Agents; D004958:Estradiol; D006426:Hemicholinium 3; D048369:MAP Kinase Kinase 1; D009466:Neuromuscular Blocking Agents; D018696:Neuroprotective Agents; D009498:Neurotoxins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011960:Receptors, Estrogen; C044894:ethylcholine aziridinium