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dc.creatorTheofilopoulos, S.en
dc.creatorTsirimonaki, E.en
dc.creatorSakellaridis, N.en
dc.creatorMangoura, D.en
dc.date.accessioned2015-11-23T10:49:56Z
dc.date.available2015-11-23T10:49:56Z
dc.date.issued2007
dc.identifier.issn10116575
dc.identifier.urihttp://hdl.handle.net/11615/33647
dc.description.abstractWe have successfully established for the first time in the literature cell lines from human fetal cells derived from the amniotic fluid (AF) and have documented that these cells may progress and stably express many of the same genes which define progenitor dopaminergic neurons. AF cells (AFCs) may thus provide an excellent model for studying the development of dopaminergic neurons. The dopaminergic and noradrenergic transcriptional program is highly regulated during development and in the adult, in response to activation of membrane receptor signalling cascades. Gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, is known to be regulated by receptors that act through protein kinase C (PKC) or Ras signaling. Therefore, we pharmacologically or genetically manipulated each signalling molecule by downregulating PKC with long term (24 h) exposure of cells to the phorbol ester TPA (12-O-tetradecanoyl-phorbol-13-acetate), by overexpressing Ras with transfection, or by downregulating activated Ras by overxepressing the GRDI domain of the neurofibromin protein, a potent Ras GAP. We found that treatment with TPA increased transcription of both TH and Nurr1 (a transcriptional 'hub' for the acquisition of a dopaminergic phenotype) by over 80%, whereas GRDI blocked almost all TH expression. Moreover, while Ras overexpression had no effect on these two genes, it induced the de novo expression of the noradrenergic phenotype marker DBH. Expression of VMAT2 increased with all molecular manipulations, while expression of several neuronal markers, namely Tau, b-tubulin, and syntaxin, was not affected by any condition. Interestingly, treatment of AFCs with cytochalasin, which disrupts microfilaments, caused a 50% decrease in Nurr1 transcript compared to control, a 4-fold increase in VMAT2 message, and a 40% decrease in Ptx3 message. Taken together, these studies suggest that PKC and Ras have important yet differential roles in regulating gene expression of the dopaminergic marker TH and noradrenergic marker DBH during neuronal progression. ©ΦAPMAKON-TÚTTOς.en
dc.source.urihttp://www.scopus.com/inward/record.url?eid=2-s2.0-34248230696&partnerID=40&md5=c8c34e375b729909ec36a81d1f5284da
dc.subjectDopaminergic marker THen
dc.subjectGene expressionen
dc.subjectNor-adrenergic marker DBHen
dc.subjectProtein kinase Cen
dc.subjectRasen
dc.subjectactin binding proteinen
dc.subjectcytochalasinen
dc.subjectdopamineen
dc.subjectdopamine receptor stimulating agenten
dc.subjectmembrane receptoren
dc.subjectnuclear receptor related factor 1en
dc.subjectpentraxin 3en
dc.subjectphorbol 13 acetate 12 myristateen
dc.subjectphorbol esteren
dc.subjectRas proteinen
dc.subjectsyntaxinen
dc.subjecttau proteinen
dc.subjecttubulinen
dc.subjecttyrosine 3 monooxygenaseen
dc.subjectvesicular monoamine transporter 2en
dc.subjectamnion fluiden
dc.subjectconference paperen
dc.subjectcontrolled studyen
dc.subjectdopaminergic nerve cellen
dc.subjectgene controlen
dc.subjectgene disruptionen
dc.subjectgene overexpressionen
dc.subjectgenetic transcriptionen
dc.subjectgenetic variabilityen
dc.subjecthumanen
dc.subjecthuman cellen
dc.subjectmarker geneen
dc.subjectnerve cell differentiationen
dc.subjectnoradrenergic nerveen
dc.subjectphenotypeen
dc.subjectprotein synthesisen
dc.subjectstem cellen
dc.titlePKC and Ras differentially regulate gene expression of the dopaminergic marker TH and noradrenergic marker DBHen
dc.typejournalArticleen


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