Document Detail


Nurr1 regulates dopamine synthesis and storage in MN9D dopamine cells.
MedLine Citation:
PMID:  12915123     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nurr1, a transcription factor belonging to the nuclear receptor family, is essential for the generation of midbrain dopamine (DA) cells during embryonic development. Nurr1 continues to be expressed in adult DA neurons but the role for Nurr1 in inducing and regulating basic dopaminergic functions such as dopamine synthesis and storage has remained unknown. We have previously used MN9D dopamine cells to analyze the role of Nurr1 and retinoids in DA cell maturation. These studies demonstrated that both Nurr1 and retinoids induce cell cycle arrest and a mature morphology. Here we used MN9D cells to investigate how Nurr1 regulates dopaminergic functions. Our results demonstrate that Nurr1, but not retinoids, increases DA content and the expression of aromatic L-amino acid decarboxylase (AADC) and vesicular monoamine transporter-2 (VMAT2) in MN9D cells. In a Nurr1-inducible cell line upregulation of VMAT2 is dependent on continuous Nurr1 expression. Moreover, AADC and VMAT2 are deregulated in midbrain DA cells of Nurr1 knockout embryos as revealed by in situ hybridization. Together, the results provide evidence indicating an instructive role for Nurr1 in controlling DA synthesis and storage.
Authors:
Elisabet Hermanson; Bertrand Joseph; Diogo Castro; Eva Lindqvist; Piia Aarnisalo; Asa Wallén; Gerard Benoit; Bastian Hengerer; Lars Olson; Thomas Perlmann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental cell research     Volume:  288     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-08-13     Completed Date:  2003-10-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  324-34     Citation Subset:  IM    
Affiliation:
Ludwig Institute for Cancer Research, Stockholm Branch, P.O. Box 240, S-171 77 Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Bacterial Agents / metabolism
Antineoplastic Agents / metabolism
Aromatic-L-Amino-Acid Decarboxylases / genetics,  metabolism
Biological Markers
Cell Line
Cell Size
DNA-Binding Proteins / genetics,  metabolism*
Dopamine / metabolism*
Doxycycline / metabolism
Embryo, Mammalian / anatomy & histology,  physiology
Female
Male
Membrane Glycoproteins / genetics,  metabolism
Membrane Transport Proteins*
Mesencephalon / cytology,  physiology
Mice
Mice, Knockout
Neuropeptides*
Nuclear Receptor Subfamily 4, Group A, Member 2
Transcription Factors / genetics,  metabolism*
Transfection
Tretinoin / metabolism
Vesicular Biogenic Amine Transport Proteins
Vesicular Monoamine Transport Proteins
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Antineoplastic Agents; 0/Biological Markers; 0/DNA-Binding Proteins; 0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Neuropeptides; 0/Nr4a2 protein, mouse; 0/Nuclear Receptor Subfamily 4, Group A, Member 2; 0/Slc18a2 protein, mouse; 0/Transcription Factors; 0/Vesicular Biogenic Amine Transport Proteins; 0/Vesicular Monoamine Transport Proteins; 302-79-4/Tretinoin; 564-25-0/Doxycycline; EC 4.1.1.28/Aromatic-L-Amino-Acid Decarboxylases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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