Document Detail


N1E-115 mouse neuroblastoma cells express MT1 melatonin receptors and produce neurites in response to melatonin.
MedLine Citation:
PMID:  11341973     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Melatonin, a pineal hormone that induces sleep, has become a popular over-the-counter drug. The cellular effects of melatonin, however, are only beginning to be studied. We have recently shown that stimulation of the MT1 melatonin receptor induces rapid and dramatic cytoskeletal rearrangements in transformed non-neuronal cells (Witt-Enderby et al., Cell. Motil. Cytoskel. 46 (2000) 28). These cytoskeletal changes result in the formation of structures that closely resemble neurites. In this work, we show that the N1E-115 mouse neuroblastoma cell line rapidly responds to melatonin stimulation and forms neurites within 24 h. We also demonstrate that these cells readily bind 2-[125I]iodomelatonin at levels consistent with what is noted for native tissues (B(max)=3.43+/-1.56 fmol/mg protein; K(d)=240 pM). Western analysis shows that these cells possess and express melatonin receptors of the MT1 subtype. Treatment with pertussis toxin eliminates neurite formation whereas treatment with the MT2 subtype-specific activator, BMNEP, does not induce neurite formation. We have previously shown that increases in MEK 1/2 and ERK 1/2 phosphorylation are correlated with the shape changes in transformed CHO cells. Western analysis of the MEK/ERK signaling pathway in N1E-115 cells shows that this pathway is most likely maximally and constitutively stimulated. This may account for the spontaneous production of neurites noted for this cell line after long culture periods. The results of this work show that melatonin receptor stimulation in a neuronal cell type results in the formation of neurites and that the receptors responsible for melatonin-induced neurite formation in N1E-115 cells are most likely of the MT1 subtype.
Authors:
S L Bordt; R M McKeon; P K Li; P A Witt-Enderby; M A Melan
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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:  Biochimica et biophysica acta     Volume:  1499     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-05-08     Completed Date:  2001-05-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  257-64     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Iodine Radioisotopes
Kinetics
Melatonin / analogs & derivatives,  metabolism,  pharmacology*
Mice
Mitogen-Activated Protein Kinase Kinases / metabolism
Mitogen-Activated Protein Kinases / metabolism
Neurites / drug effects*,  ultrastructure*
Neuroblastoma / metabolism*,  ultrastructure*
Neurons / drug effects,  metabolism,  ultrastructure
Pertussis Toxin
Receptors, Cell Surface / agonists,  metabolism*
Receptors, Cytoplasmic and Nuclear / agonists,  metabolism*
Receptors, Melatonin
Tumor Cells, Cultured
Virulence Factors, Bordetella / pharmacology
Grant Support
ID/Acronym/Agency:
DK54070/DK/NIDDK NIH HHS; NS37672/NS/NINDS NIH HHS; NS38873/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Iodine Radioisotopes; 0/Receptors, Cell Surface; 0/Receptors, Cytoplasmic and Nuclear; 0/Receptors, Melatonin; 0/Virulence Factors, Bordetella; 73-31-4/Melatonin; 93515-00-5/2-iodomelatonin; EC 2.4.2.31/Pertussis Toxin; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases

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


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