Nongenomic antiapoptotic signal transduction by estrogen in cultured cortical neurons

Citation
K. Honda et al., Nongenomic antiapoptotic signal transduction by estrogen in cultured cortical neurons, J NEUROSC R, 64(5), 2001, pp. 466-475
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE RESEARCH
ISSN journal
0360-4012 → ACNP
Volume
64
Issue
5
Year of publication
2001
Pages
466 - 475
Database
ISI
SICI code
0360-4012(20010601)64:5<466:NASTBE>2.0.ZU;2-R
Abstract
Estrogen replacement therapy in menopausal women has been suggested to be b eneficial in preventing the progression of cognitive impairment in Alzheime r disease. We demonstrated previously that the phosphatidylinositol 3-kinas e (P13-K)/Akt signal transduction pathway plays a pivotal role on the neuro protection provided by 17 beta -estradiol against acute glutamate toxicity. In the present study, we investigated the mechanism of neuroprotection aga inst apoptosis because acute glutamate toxicity predominantly induced necro sis, 17 beta -estradiol provided neuroprotection against apoptosis induced by staurosporine. This neuroprotection was inhibited by pretreatment with a P13-K inhibitor, LY294002. An estrogen receptor specific antagonist, ICI18 2780, also suppressed the neuroprotection provided by 17 beta -estradiol, W estern blotting analysis demonstrated that treatment with 17 beta -estradio l induced the phosphorylation of Akt within 5 min, which was suppressed by pretreatment with LY294002 and ICI182780, Furthermore, 17 beta -estradiol i nduced phosphorylation of the cAMP response element binding protein (CREB) at Ser(133) within 15 min and then upregulated Bcl-2 in a P13-K/Akt-depende nt manner. Because CREB is known to be a transcription factor for Bcl-2, th ese results suggest that 17 beta -estradiol exerts its antiapoptotic effect s by CREB phosphorylation and Bcl-2 upregulation via nongenomic activation of the P13-K/Akt pathway in cultured cortical neurons. (C) 2001 Wiley-Liss. Inc.