کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9425755 | 1295890 | 2005 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
17β-estradiol induced Ca2+ influx via L-type calcium channels activates the Src/ERK/cyclic-AMP response element binding protein signal pathway and BCL-2 expression in rat hippocampal neurons: A potential initiation mechanism for estrogen-induced neuropro
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
N-methyl-d-aspartateCalcium-channelscyclic-AMP response element binding proteinPI3-KPKCCREBNMDACaMKIIERK17β-estradiol - 17β استرادیولsiRNA - siRNA[Ca2+]i - [Ca2 +] iω-agatoxin IVA - ω-آگاتوکسین IVAω-conotoxin GVIA - ω-کنوتوکسین GVIAAkt - آکتsmall interference RNA - تداخل کوچک RNAintracellular Ca2+ concentration - غلظت Ca2 + داخل سلولیphosphatidylinositol-3-kinase - فسفاتیدیلینواستیل-3-کینازprotein kinase B - پروتئین کیناز BProtein kinase C - پروتئین کیناز سیextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیEstrogen receptor - گیرنده استروژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Our group and others have demonstrated that 17β-estradiol (E2) induces neurotrophic and neuroprotective responses in hippocampal and cortical neurons which are dependent upon the Src/extracellular signal-regulated kinase (ERK) signaling pathways. The purpose of this study was to determine the upstream mechanism(s) that initiates the signaling cascade leading to E2-inducible neuroprotection. We tested the hypothesis that E2 activates rapid Ca2+ influx in hippocampal neurons, which would lead to activation of the Src/ERK signaling cascade and up-regulation of Bcl-2 protein expression. Using fura-2 ratiometric Ca2+ imaging, we demonstrated that E2 induced a rapid rise of intracellular Ca2+ concentration ([Ca2+]i) within minutes of exposure which was blocked by an L-type Ca2+ channel antagonist. Inhibition of L-type Ca2+ channels resulted in a loss of E2 activation of the Src/ERK cascade, activation of cyclic-AMP response element binding protein (CREB) and subsequent increase in Bcl-2. Real-time intracellular Ca2+ imaging combined with pERK immunofluorescence, demonstrated that E2 induced [Ca2+]i was coincident with ERK activation in the same neuron. Small interfering RNA knockdown of CREB resulted in a loss of E2 activation of CREB and subsequent E2-induced increase of Bcl-2 expression. We further demonstrated the presence of specific membrane E2 binding sites in hippocampal neurons. Together, these data indicate that E2-induced Ca2+ influx via the L-type Ca2+ channel is required for E2 activation of the Src/ERK/CREB/Bcl-2 signaling. Implications of these data for understanding estrogen action in brain and use of estrogen therapy for prevention of neurodegenerative disease are discussed.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 135, Issue 1, 2005, Pages 59-72
Journal: Neuroscience - Volume 135, Issue 1, 2005, Pages 59-72
نویسندگان
T.-W. Wu, J.M. Wang, S. Chen, R.D. Brinton,