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    標題: Curcuminoids Promote Neurite Outgrowth in PC12 Cells through MAPK/ERK- and PKC-Dependent Pathways
    作者: Liao, Kuo-Kai
    Wu, Ming-Jiuan
    Chen, Pei-Yi
    Huang, Szu-Wei
    Chiu, Shu-Jun
    Ho, Chi-Tang
    Yen, Jui-Hung
    貢獻者: 生物科技系
    關鍵字: Curcuminoids
    Pc12 Cells
    Neurite Outgrowth
    Erk1/2
    Pkc
    Creb
    日期: 2012-01-11
    上傳時間: 2014-03-21 16:18:00 (UTC+8)
    出版者: Amer Chemical Soc
    摘要: Curcuminoids, the predominant polyphenolic compounds in the rhizome of Curcuma longa Linn., consist of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). They exhibit multiple desirable characteristics for a neuroprotective agent including antioxidant, anti-inflammatory, and antiamyloid activities. In this work, we report the first investigation of the neurotrophic action and mechanism of curcuminoids in PC12 cells, which respond to nerve growth factor (NGF) and therefore serve as a model system for primary neuronal cells. The percentages of neurite-bearing cells for those treated with 20 mu M curcumin, DMC, and BDMC for 72 h reached 21.6 +/- 2.0%, 16.3 +/- 2.4%, and 19.9 +/- + 2.5%, respectively, and were significantly higher than that of the negative control (2.0 +/- 0.3%, p < 0.05). In parallel, increased expression of the neuronal differentiation markers, growth-associated protein-43 (GAP-43), and neurofilament-L (NF-L) was found in curcuminoid-treated cells. All three curcuminoids (20 mu M) activated extracellular signal-regulated protein kinase 1/2 (ERK1/2) and protein kinase C (PKC) signalings, and inhibition of these kinases with the respective pharmacological inhibitors effectively attenuated curcuminoid-induced neurite outgrowth. Furthermore, our results show that both curcumin and DMC, but not BDMC, induced phosphorylation of cAMP response element-binding protein (CREB) and CRE-reporter gene activity significantly (p < 0.05). These inductions were markedly attenuated by the addition of MEK/ERK or PKC inhibitor; as a consequence, ERK- and PKC-dependent pathways may be involved in curcuminoid-mediated neuritogenesis in PC12 cells. Moreover, activation of CREB coupling with CRE-dependent gene transcription may play a vital role for curcumin- or DMC-induced PC12 differentiation.
    關聯: Journal of Agricultural And Food Chemistry, 60(1), 433-443
    顯示於類別:[生物科技系(所)] 期刊論文

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