Restoration of impaired phosphorylation of cyclic AMP response element‐binding protein (CREB) by EGb 761 and its constituents in Aβ‐expressing neuroblastoma cells
Restoration of impaired phosphorylation of cyclic AMP response element‐binding protein (CREB) by EGb 761 and its constituents in Aβ‐expressing neuroblastoma cells
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DOI：
10.1111/j.1460-9568.2007.05905.x
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发表时间：
2007-11
影响因子：
3.4
通讯作者：
Yanan Xu;Changhai Cui;Cheuk Pang;Y. Christen;Yuan Luo
中科院分区：
文献类型：
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作者：
Yanan Xu;Changhai Cui;Cheuk Pang;Y. Christen;Yuan Luo
环磷酸腺苷反应元件结合蛋白（CREB）在阿尔茨海默病（AD）的神经元可塑性和淀粉样β肽（Aβ）诱导的认知障碍中起重要作用。在这里，我们证明了银杏叶提取物，EGb 761，显示通过激活CREB信号通路的神经元保护作用。在含有细胞分泌的A β的条件培养基中培养的野生型神经母细胞瘤细胞表现出磷酸化CREB（pCREB）水平降低。向条件培养基中加入EGb 761（100 µg/mL）或抗寡聚体特异性抗体（A-11）可恢复pCREB水平。在表达A β的神经母细胞瘤细胞系中，EGb 761处理增加了pCREB和脑源性神经营养因子的水平。CREB的上游信号通路，包括蛋白激酶C、ERK、核糖体S6激酶（RSK）90和一氧化氮通路的抑制剂可阻断EGb 761诱导的CREB磷酸化。此外，这些抑制剂差异阻断EGb 761，银杏内酯C，槲皮素和白果内酯，这表明不同的影响EGb 761个别成分的个别成分的影响。单个EGb 761组分的作用为EGb 761增强AD患者认知能力的直接机制提供了进一步的见解。
Cyclic AMP response element‐binding protein (CREB) plays important roles in neuronal plasticity and amyloid β‐peptide (Aβ)‐induced cognitive impairment in Alzheimer's disease (AD). Here we demonstrated that Ginkgo biloba extract, EGb 761, displayed the neuron protective effect by activating the CREB signaling pathway. Wild‐type neuroblastoma cells cultured in a conditioned medium containing cell‐secreted Αβ exhibited reduced levels of phosphorylated CREB (pCREB). Addition of EGb 761 (100 µg/mL) or an anti‐oligomer‐specific antibody (A‐11) to the conditioned medium could restore pCREB level. In a neuroblastoma cell line expressing Αβ, treatment with EGb 761 increased levels of pCREB and brain‐derived neurotrophic factor. Furthermore, CREB phosphorylation induced by EGb 761 was blocked by inhibitors of several upstream signaling pathways of CREB, including protein kinase C, ERK, ribosomal S6 kinase(RSK)90 and nitric oxide pathway. Moreover, these inhibitors differentially blocked the effects of individual components of EGb 761, ginkgolide C, quercetin and bilobalide, which suggest diverse effects of the EGb 761 individual components. Actions of individual EGb 761 components provide further insights into direct mechanisms underlying the effect of EGb 761 on enhancing the cognitive performance of patients with AD.