國家衛生研究院 NHRI:Item 3990099045/1289

NHRI > Institute of Biomedical Engineering and Nanomedicine > Chung-Shi Yang > Periodical Articles > Item 3990099045/1289

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/1289

Title:	Inhibitory regulation of glutamate aspartate transporter (GLAST) expression in astrocytes by cadmium-induced calcium influx
Authors:	Liu, YP;Yang, CS;Tzeng, SF
Contributors:	Center for Nanomedicine Research
Abstract:	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.
Keywords:	Biochemistry & Molecular Biology;Neurosciences
Date:	2008-04
Relation:	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
Appears in Collections:	[Chung-Shi Yang] Periodical Articles

Files in This Item:

File	Description	Size	Format
000254383800012.pdf		969Kb	Adobe PDF	368	View/Open

Loading...