Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 (0.1muM), an inhibitor of phosphatidylinositol 3-kinase (PI3-K) and forskolin (10, 25muM), 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 (0.01muM) 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-3beta) 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.
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PMID:Inhibitory effect of imipramine on the human corticotropin-releasing-hormone gene promoter activity operates through a PI3-K/AKT mediated pathway. 1599 64


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