| GDNF signaling in embryonic midbrain neurons in vitro. | |
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MedLine Citation:
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PMID: 17574220 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The glial cell line-derived neurotrophic factor (GDNF) exerts trophic actions on a number of cell types, including mesencephalic dopaminergic (mDA) neurons. Using rat mesencephalic primary cultures enriched in mDA neurons, we show that protracted GDNF stimulation increases their survival and neurite outgrowth. It modulates the expression of genes essential for DA function (tyrosine hydroxylase, TH and dopamine transporter, dat) and of DA high affinity uptake. To identify genes involved in GDNF signaling pathways, we have used DNA microarray on mDA cultures stimulated with GDNF for 3 h. Here we show that GDNF signaling sequentially activates the genes encoding for the transcription factors EGR1 and TIEG. In addition, it increases the expression of cav1, which encodes for the major component of caveolae. GDNF also modulates the expression of the genes encoding for the Calcineurin subunits ppp3R1 and ppp3CB, and inhibits calcium-calmodulin-dependent protein kinase II beta isoform (CaMKIIbeta) gene expression. These proteins are involved in neuronal differentiation and synaptic plasticity. Moreover, GDNF stimulation down regulates the expression of the glycogen synthase kinase 3beta (gsk3beta) gene, involved in neuronal apoptosis. Using inhibitors of specific intracellular signal transduction pathways we show that changes of egr1, tieg, cav1, CaMkIIbeta and gsk3beta genes expression are extracellular-signal regulated kinases 1/2 (ERK)-dependent, while the cAMP-dependent protein kinase (PKA) pathway influences the up-regulation of ppp3R1 and ppp3CB gene expression. These results demonstrate that GDNF stimulation results in the transcriptional modulation of genes involved in neuronal plasticity and survival and in mDA function, mediated in part by ERK and PKA signaling. |
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Authors:
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Claudia Consales; Floriana Volpicelli; Dario Greco; Luigi Leone; Luca Colucci-D'Amato; Carla Perrone-Capano; Umberto di Porzio |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-05-05 |
Journal Detail:
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Title: Brain research Volume: 1159 ISSN: 0006-8993 ISO Abbreviation: Brain Res. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-07-20 Completed Date: 2007-10-12 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 28-39 Citation Subset: IM |
Affiliation:
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Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, via P. Castellino 111, 80131 Naples, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Dopamine / metabolism Dopamine Plasma Membrane Transport Proteins / genetics, metabolism Dose-Response Relationship, Drug Embryo, Mammalian Enzyme Inhibitors / pharmacology Female Gene Expression Regulation / drug effects, physiology Glial Cell Line-Derived Neurotrophic Factor / pharmacology, physiology* Mesencephalon / cytology*, embryology Microarray Analysis / methods Nerve Tissue Proteins / genetics, metabolism Neurons / drug effects, physiology* Pregnancy RNA, Messenger / metabolism Rats Rats, Sprague-Dawley Signal Transduction / drug effects, physiology* Time Factors Tritium / metabolism Tyrosine 3-Monooxygenase / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Dopamine Plasma Membrane Transport Proteins; 0/Enzyme Inhibitors; 0/Glial Cell Line-Derived Neurotrophic Factor; 0/Nerve Tissue Proteins; 0/RNA, Messenger; 10028-17-8/Tritium; EC 1.14.16.2/Tyrosine 3-Monooxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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