國家衛生研究院 NHRI:Item 3990099045/1289
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    題名: Inhibitory regulation of glutamate aspartate transporter (GLAST) expression in astrocytes by cadmium-induced calcium influx
    作者: Liu, YP;Yang, CS;Tzeng, SF
    貢獻者: Center for Nanomedicine Research
    摘要: After injury to the CNS, the accumulation of extracellular glutamate induces neuronal excitotoxicity, leading to secondary tissue damage. Astrocytes can reduce excess extracellular glutamate primarily through the astrocytic glutamate transporter-1 and the Na+-dependent glutamate/aspartate transporter (GLAST). In this study, we used an in vitro model of cadmium-induced cellular stress and found that glutamate uptake activity of astrocytes was suppressed because of cadmium-induced inhibition of GLAST expression. The blockage of cadmium-triggered Ca2+ influx by Ca2+ chelators elevated GLAST transcription and glutamate uptake activity in astrocytes, suggesting that the suppression of GLAST expression in cadmium-treated astrocytes was Ca2+-dependent. This was supported by the findings showing the reduction of GLAST mRNA in astrocytes after treatment with Ca2+-ionophore A23187. Cadmium reduced human GLAST promoter activity; however, it increased the binding of Ca2+-sensitive activator protein-1 (AP-1) and cAMP response element binding protein (CREB) to their specific elements derived from the human GLAST promoter. These results demonstrate that AP-1 and CREB may be coupled with Ca2+-dependent pathway triggered by cadmium to mediate the inhibition of GLAST transcription. Our results suggest that Ca2+ influx into astrocytes after CNS injury could cause the down-regulation of GLAST expression, thus reducing the astrocytic glutamate uptake function, which in turn may exacerbate secondary damage after CNS injury.
    關鍵詞: Biochemistry & Molecular Biology;Neurosciences
    日期: 2008-04
    關聯: Journal of Neurochemistry. 2008 Apr;105(1):137-150.
    Link to: http://dx.doi.org/10.1111/j.1471-4159.2007.05118.x
    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:000254383800012
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=41149181234
    顯示於類別:[楊重熙] 期刊論文

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