کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2553670 | 1560751 | 2008 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Multisignal regulation of the rat NMDA1 receptor subunit gene — A pivotal role of glucocorticoid-dependent transcription Multisignal regulation of the rat NMDA1 receptor subunit gene — A pivotal role of glucocorticoid-dependent transcription](/preview/png/2553670.png)
Although excess of glucocorticoid causes neuronal damage with cognitive disorders, the molecular mechanism for this remains unclear. In this study, we examined the effect of adrenal corticosteroids on the transcription of NMDA glutamate receptor subunit genes and Alzheimer disease-related genes such as amyloid precursor protein (APP), β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), and presenilin using neuronal cell lines in vitro. We found that synthetic glucocorticoid dexamethasone (dex) potently increased the promoter activity of NMDA1 and 2A subunit genes, but did not stimulate those of Alzheimer disease-related genes. The similar effect of dex was observed on intrinsic NMDA1 mRNA and protein expression. Furthermore, dex showed synergistic and additive effects with protein kinase A- and C-mediated signaling pathways, respectively. Finally, treatment of the Neuro2A cells, which express intrinsic glucocorticoid receptor, with dex significantly enhanced the glutamate-induced neurotoxicity. Our results suggest that glucocorticoid-induced neuronal damage may be, at least partly, attributable to enhanced expression of glutamate NMDA receptor with a resultant increase in the susceptibility of glutamate-induced excitotoxicity rather than to a direct effect of the hormone to the Alzheimer disease-related genes.
Journal: Life Sciences - Volume 82, Issues 23–24, 6 June 2008, Pages 1137–1141