Document Detail

Delta opioid peptide DADLE and naltrexone cause cell cycle arrest and differentiation in a CNS neural progenitor cell line.
MedLine Citation:
PMID:  19953654     Owner:  NLM     Status:  MEDLINE    
Opioids have been demonstrated to play an important role in CNS development by affecting proliferation and differentiation in various types of neural cells. This study examined the effect of a stable delta opioid peptide [D-Ala(2), D-Leu(5)]-enkephalin (DADLE) on proliferation and differentiation in an AF5 CNS neural progenitor cell line derived from rat mesencephalic cells. DADLE (1 pM, 0.1 nM, or 10 nM) caused a significant growth inhibition on AF5 cells. The opioid antagonist naltrexone at 0.1 nM also caused growth inhibition in the same cells. When DADLE and naltrexone were both added to the AF5 cells, the resultant growth inhibition was apparently additive. DADLE alone or DADLE in combination with naltrexone did not cause apoptosis as evidenced by negative TUNEL staining. The cell-cycle progression analysis indicated that both DADLE (0.1 nM) and naltrexone (0.1 nM) caused an arrest of AF5 cell cycle progression at the G1 checkpoint. Neuronal marker indicated that DADLE- or naltrexone-treated AF5 cells tend to differentiate more when compared to controls. Results demonstrate the nonopioid action of both DADLE and naltrexone on cell cycle arrest and differentiation in a CNS neural progenitor cell line. Results also suggest some potential utilization of DADLE and/or naltrexone in stem cell research.
Shang-Yi Tsai; Chung-Ting Lee; Teruo Hayashi; William J Freed; Tsung-Ping Su
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Synapse (New York, N.Y.)     Volume:  64     ISSN:  1098-2396     ISO Abbreviation:  Synapse     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-02-12     Completed Date:  2010-05-10     Revised Date:  2011-08-25    
Medline Journal Info:
Nlm Unique ID:  8806914     Medline TA:  Synapse     Country:  United States    
Other Details:
Languages:  eng     Pagination:  267-73     Citation Subset:  IM    
Cellular Pathobiology Section, Cellular Neurobiology Research Branch, Intramural Research Program, NIDA, NIH, DHHS, Baltimore, Maryland 21224, USA.
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MeSH Terms
Analysis of Variance
Apoptosis / drug effects
Cell Cycle / drug effects*
Cell Differentiation / drug effects*
Cell Line
Cell Proliferation / drug effects
DNA Fragmentation / drug effects
Dose-Response Relationship, Drug
Drug Interactions
Enkephalin, Leucine-2-Alanine / pharmacology*
Flow Cytometry / methods
In Situ Nick-End Labeling / methods
Naltrexone / analogs & derivatives*,  pharmacology
Neurons / drug effects,  physiology*
Stem Cells / drug effects*
Time Factors
Tubulin / metabolism
Grant Support
Reg. No./Substance:
0/Tubulin; 16590-41-3/Naltrexone; 63631-40-3/Enkephalin, Leucine-2-Alanine; 73674-86-9/naltrexazone

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

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