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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/27892


    標題: Neurotrophic Action of 5-Hydroxylated Polymethoxyflavones: 5-Demethylnobiletin and Gardenin A Stimulate Neuritogenesis in PC12 Cells
    作者: Chiu, Szu-Ping
    Wu, Ming-Jiuan
    Chen, Pei-Yi
    Ho, Yi-Ru
    Tai, Mi-Hsueh
    Ho, Chi-Tang
    Yen, Jui-Hung
    貢獻者: 生物科技系
    關鍵字: Polymethoxyflavones
    5-Demethylnobiletin
    Gardenin A
    Pc12 Cells
    Neurite Outgrowth
    日期: 2013-10
    上傳時間: 2014-05-26 10:47:54 (UTC+8)
    出版者: Amer Chemical Soc
    摘要: Polymethoxyflavones (PMFs) exhibit a broad spectrum of biological properties, including anticancer, antiatherogenic, and neuroprotective effects. The aim of this study is to investigate the neurotrophic effects of 5-demethylnobiletin, a hydroxylated PMF found in citrus plants, and gardenin A, a synthetic PMF analogue, on neurite outgrowth and neuronal differentiation in PC12 cells. The results of this study showed that 5-demethylnobiletin and gardenin A (10-20 mu M) potently induce neurite outgrowth in PC12 cells, accompanied by the expression of neuronal differentiation and synapse formation marker proteins, growth associated protein-43 (GAP-43), and synaptophysin. We observed that the addition of K252a, a TrKA antagonist, significantly inhibited NGF-induced neurite outgrowth in PC12 cells, but 5-demethylnobiletin- or gardenin A-induced neurite outgrowth was not affected. Treatment with 5-demethylnobiletin and gardenin A markedly induced the phosphorylation of both cyclic AMP response element-binding protein (CREB) and CRE-mediated transcription, which was suppressed through the administration of the inhibitor 2-naphthol AS-E phosphate (KG-501) or. using CREB siRNA. Furthermore, our results showed that MAPK/ERK kinase 1/2 (MEK1/2), protein kinase A (PKA), and protein kinase C (PKC) inhibitors blocked the CRE transcription activity and neurite outgrowth induced through 5-demethylnobiletin or gardenin A. Consistently, increased ERK phosphorylation and PKA and PKC activities were observed in PC12 cells treated with 5-demethylnobiletin or gardenin A. These results reveal for the first time that 5-demethylnobiletin and gardenin A promote neuritogenesis through the activation of MAPK/ERK-, PKC-, and PICA dependent, but not TrkA-dependent, CREB signaling pathways in PC12 cells.
    關聯: Journal of Agricultural And Food Chemistry, v.61 n.39 pp.9453-9463
    Appears in Collections:[生物科技系(所)] 期刊論文

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