國家衛生研究院 NHRI:Item 3990099045/7226
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    題名: The mood stabilizer valproate activates human FGF1 gene promoter through inhibiting HDAC and GSK-3 activities
    作者: Kao, CY;Hsu, YC;Liu, JW;Lee, DC;Chung, YF;Chiu, IM
    貢獻者: Institute of Cellular and Systems Medicine
    摘要: Valproic acid (VPA) is the primary mood-stabilizing drug to exert neuroprotective effects and to treat bipolar disorder in clinic. Fibroblast growth factor 1 (FGF1) has been shown to regulate cell proliferation, cell division and neurogenesis. Human FGF1 gene 1B promoter (-540 to +31)-driven green fluorescence (F1BGFP) has been shown to recapitulate endogenous FGF1 gene expression and facilitates the isolation of neural stem/progenitor cells (NSPCs) from developing and adult mouse brains. In this study, we provide several lines of evidence to demonstrate the underlying mechanisms of VPA in activating FGF-1B promoter activity: (i) VPA significantly increased the FGF-1B mRNA expression and the percentage of F1BGFP(+) cells; (ii) the increase of F1BGFP expression by VPA involves changes of RFX1-3 transcriptional complexes and the increase of histone H3 acetylation on the 18-bp cis-element of FGF-1B promoter; (iii) treatments of other HDAC inhibitors, sodium butyrate and trichostatin A, significantly increased the expression levels of FGF-1B, RFX2 and RFX3 transcripts; (iv) treatments of GSK-3 inhibitor, lithium, or GSK-3 siRNAs also significantly activated FGF-1B promoter; (v) VPA specifically enhanced neuronal differentiation in F1BGFP(+) embryonic stem cells and NSPCs rather than GFP(-) cells. This study suggested, for the first time, that VPA activates human FGF1 gene promoter through inhibiting HDAC and GSK-3 activities.
    日期: 2013-07
    關聯: Journal of Neurochemistry. 2013 Jul;126(1):4-18.
    Link to: http://dx.doi.org/10.1111/jnc.12292
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-3042&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000320722700002
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84879410872
    顯示於類別:[邱英明] 期刊論文

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