کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9892023 | 1541094 | 2005 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identification by microarray analysis of aspartate aminotransferase and glutamine synthetase as glucocorticoid target genes in a mouse Schwann cell line
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کلمات کلیدی
DEXCATGREEREcytosolic aspartate aminotransferase - آسپارتات آمینوترانسفراز سیتوزولEstradiol - استرادیولDexamethasone - دگزامتازونestrogen response element - عنصر پاسخ استروژنGlucocorticoid response element - عنصر پاسخ گلوکوکورتیکوئیدchloramphenicol acetyltransferase - کلرامفنیکول استیل ترانسفرازAndrogen Receptor - گیرنده آندروژنیEstrogen receptor - گیرنده استروژنglucocorticoid receptor - گیرنده گلوکوکورتیکوئید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Schwann cells have been identified as targets for glucocorticoids. Besides genes implicated in the myelination process, the target genes of glucocorticoids have not been identified in these cells. For that purpose, we performed microarray analysis on MSC80 (mouse Schwann cells) treated with a synthetic glucocorticoid, dexamethasone. These cells express a functional glucocorticoid receptor (GR), but none of the other steroid receptors. This allowed us to identify genes specifically regulated by GR in the absence of the mineralocorticoid receptor. Among the 5000 genes analyzed, 12 were at least two-fold upregulated and 91 genes were at least two-fold down-regulated upon treatment with dexamethasone. Because of their potential role in Schwann cell homeostasis, we selected, for further analysis, the upregulated genes encoding glutamine synthetase (GS) and cytosolic aspartate aminotransferase (cAspAT). These genes play a crucial role in the glutamate cycle which was shown to be vital in neuron-astrocyte cross-talk in the central nervous system. Their activation was confirmed by semi-quantitative and real-time PCR. A detailed analysis of cAspAT promoter activity revealed that the mechanism of regulation by GR in Schwann cells differs from that in hepatoma cells, suggesting a cell-specific regulation. The transactivation potency of the two Glucocorticoid Responsive Units (GRU) present in the cAspAT promoter seems to be dependent on the levels of the GR in MSC80 cells. Furthermore, we show that an increase in GR levels under certain circumstances could considerably potentiate the effects of glucocorticoids on the cAspAT promoter via synergistic activation of both GRU, To the opposite, an enhancement in GR levels did not further potentiate Dex-activation of the GS promoter, showing a differential mechanism of action of GR in the context of both promoters.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 97, Issue 4, December 2005, Pages 342-352
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 97, Issue 4, December 2005, Pages 342-352
نویسندگان
Julien Grenier, Céline Tomkiewicz, Amalia Trousson, Krzysztof M. Rajkowski, Michael Schumacher, Charbel Massaad,