Proteomic analysis of embryonic stem cell-derived neural cells exposed to the antidepressant paroxetine

作者: Patrick C McHugh , Geraldine R Rogers , Barbara Loudon , Dylan M Glubb , Peter R Joyce

DOI: 10.1002/JNR.21482

关键词:

摘要: Antidepressant drugs can have significant effects on the mood of a patient suffering from major depression or other disorders. The pharmacological actions these generally affect uptake metabolism neurotransmitters serotonin, noradrenalin, and, to lesser extent, dopamine. However, many aspects antidepressant action are not understood. We conducted proteomic analysis in neuronal cell culture model an attempt identify molecules important operation pathways functionally relevant action. involved generating cultures containing mixed neural and glial cells by controlled differentiation mouse embryonic stem cells, followed exposure 1 μM paroxetine for 14 days. After exposure, we observed increased expression modification sepiapterin reductase (SPR), heat shock protein 9A, RAS EF-hand domain containing, disulfide isomerase associated 3 decreased creatine kinase, actin, prohibitin, T-cell receptor α chain, defensin-related cryptdin 5, intermediate filament proteins fibrillary acidic vimentin. SPR, most strongly up-regulated observed, controls production tetrahydrobiopterin, essential cofactor synthesis including making it plausible intriguing candidate involvement control drug SPR identified may represent links molecular processes importance dysregulation control, their respective genes be novel candidates study pharmacogenetics.

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