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    題名: Brain-Derived Neurotrophic Factor Enhances Bcl-xL Expression Through Protein Kinase Casein Kinase 2-Activated and Nuclear Factor Kappa B-Mediated Pathway in Rat Hippocampus
    作者: 趙知章
    Chao, Chih Chang;Chiang,CH;Ma,YL;Lee,EH
    貢獻者: 神科所
    關鍵詞: Bcl-xL;brain-derived neurotrophic factor;casein kinase 2;hippocampus;neuroprotection;NF-kB
    日期: 2011.05
    上傳時間: 2014-09-23 12:25:04 (UTC+8)
    摘要: Brain-derived neurotrophic factor (BDNF) was shown to produce its neuroprotective effect through extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol-3 kinase (PI3-K) signaling. But whether other pathways also mediate the neuroprotective effect of BDNF is less known. In this study, we found that direct administration of BDNF to rat hippocampal CA1 area dose-dependently increased the mRNA and protein levels of Bcl-xL. BDNF also increased protein kinase casein kinase II (CK2) activity and NF-kB phosphorylation at Ser529 dose-dependently. Further, transfection of the wild-type CK2a DNA to CA1 neurons increased nuclear factor kappa B (NF-kB) phosphorylation and Bcl-xL mRNA expression, whereas transfection of CK2a156A, the catalytically inactive mutant of CK2a, decreased these measures. Moreover, transfection of CK2a small interfering RNA (siRNA) blocked the enhancing effect of BDNF on NF-kB phosphorylation and Bcl-xL expression. These results were further confirmed by treatment of 4,5,6,7tetrabromobenzotriazole (TBB), a specific CK2 inhibitor. Transfection of NF-kBS529A, the dominant negative mutant of NF-kB, prevented the enhancing effect of BDNF on Bcl-xL expression. More importantly, BDNF activation of CK2 is not affected by co-administration of the ERK1/2 inhibitor, PD98059, and the PI3-K inhibitor, LY294002. These results demonstrate a novel BDNF signaling pathway and provide an alternative therapeutic strategy for the protective effect of BDNF on hippocampal neurons in vivo.
    關聯: Brain Pathology,21(2),150-162
    資料類型: article
    DOI 連結: http://dx.doi.org/10.1111/j.1750-3639.2010.00431.x
    DOI: 10.1111/j.1750-3639.2010.00431.x
    顯示於類別:[神經科學研究所 ] 期刊論文

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