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Inhibitory regulation of glutamate aspartate transporter (GLAST) expression in astrocytes by cadmium-induced calcium influx
| Content Provider | Scilit |
|---|---|
| Author | Liu, Yu-Peng Yang, Chung-Shi Tzeng, Shun-Fen |
| Copyright Year | 2008 |
| Description | Journal: Journal of Neurochemistry [[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 |
| Related Links | http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2007.05118.x/pdf |
| Ending Page | 150 |
| Page Count | 14 |
| Starting Page | 137 |
| e-ISSN | 14714159 |
| DOI | 10.1111/j.1471-4159.2007.05118.x |
| Journal | Journal of Neurochemistry |
| Issue Number | 1 |
| Volume Number | 105 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2008-04-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Neurochemistry Biochemistry and Molecular Biology Glutamate Transporter Glutamate Uptake Na+‐dependent Glutamate/aspartate Transporter |
| Content Type | Text |
| Resource Type | Article |
