کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8998258 | 1115615 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibitory effect of imipramine on the human corticotropin-releasing-hormone gene promoter activity operates through a PI3-K/AKT mediated pathway
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Antidepressant drugs inhibit the corticotropin-releasing-hormone (CRH) gene promoter activity in the differentiated Neuro-2A cells, but a molecular mechanism of their action has been poorly recognized. The aim of the present study was to elucidate the involvement of some intracellular signal transduction pathways in imipramine-induced inhibition of CRH gene activity in the differentiated Neuro-2A cells, stably transfected with a human CRH promoter fragment linked to the chloramphenicol acetyltransferase (CAT) reporter gene. It was found that wortmannin (0.1 μM), an inhibitor of phosphatidylinositol 3-kinase (PI3-K) and forskolin (10, 25 μM), an activator of adenylate cyclase enhanced the basal activity of CRH gene promoter, whereas inhibitors of protein kinase A, calcium/calmodulin kinase (CaMK) and mitogen-activated protein kinase (MAPK) had opposite effects. Moreover, wortmannin at a low concentration (0.01 μM) significantly reversed the inhibitory effect of imipramine on CRH-CAT activity, whereas other protein kinase inhibitors were inactive or even enhanced the imipramine effects. The involvement of PI3-K/Akt pathway in the imipramine action was confirmed by Western blot study, which showed that this drug increased phospho-Ser-473 Akt level, but had no effect on total Akt and glycogen synthase kinase (GSK-3β) levels. These results indicate that the inhibitory effect of imipramine on the CRH gene promoter activity in Neuro-2A cells is mainly connected with enhancement of PI-3K/Akt pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 49, Issue 2, August 2005, Pages 156-164
Journal: Neuropharmacology - Volume 49, Issue 2, August 2005, Pages 156-164
نویسندگان
Agnieszka Basta-Kaim, BogusÅawa Budziszewska, Lucylla Jaworska-Feil, Magdalena Tetich, Marta Kubera, Monika LeÅkiewicz, WÅadysÅaw LasoÅ,