Document Detail


Neurotrophic actions of novel compounds designed from cyclopentenone prostaglandins.
MedLine Citation:
PMID:  11279261     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previously we found that some cyclopentenone prostaglandin derivatives promoted neurite outgrowth from PC12 cells and dorsal root ganglia explants in the presence of nerve growth factor; and so we referred to them as neurite outgrowth-promoting prostaglandins (NEPPs). In this study, NEPPs protected HT22 cells against oxidative glutamate toxicity. NEPP6, one of the most effective promoters of neurite outgrowth in PC12 cells, protected the cells most potently among NEPPs 1--10. Several derivatives, NEPPs 11--19, were newly synthesized based on the chemical structure of NEPP6. NEPP11 had a more potent neuroprotective effect than NEPP6. NEPP11 also prevented the death of cortical neurons induced by various stimuli and reduced ischemic brain damage in mice. Biotinylated compounds of NEPPs were synthesized to investigate their cellular accumulation. NEPP6-biotin protected the cells and emitted potent signals from the cells. In contrast, biotinylated non-neuroprotective derivatives emitted much weaker signals. These results suggest that NEPPs are novel types of neurotrophic compounds characterized by their dual biological activities of promoting neurite outgrowth and preventing neuronal death and that their accumulation in the cells is closely associated with their neuroprotective actions.
Authors:
T Satoh; K Furuta; K Tomokiyo; S Namura; D Nakatsuka; Y Sugie; Y Ishikawa; H Hatanaka; M Suzuki; Y Watanabe
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  77     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-03-30     Completed Date:  2001-05-03     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  50-62     Citation Subset:  IM    
Affiliation:
Department of Neuroscience, Osaka Bioscience Institute, Suita-shi, Osaka, Japan. tsatoh@obi.or.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Biotin / analogs & derivatives,  chemistry,  pharmacology
Brain Ischemia / drug therapy
Cell Survival / drug effects
Cells, Cultured
Cyclopentanes / chemistry
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Mice
Microinjections
Nerve Growth Factors / administration & dosage,  chemistry,  pharmacology*
Neurites / drug effects
Neurons / cytology,  drug effects*
Neuroprotective Agents / administration & dosage,  chemistry,  pharmacology*
Prostaglandin D2 / analogs & derivatives
Prostaglandins / administration & dosage,  chemistry,  pharmacology*
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Cyclopentanes; 0/NEPP11 compound; 0/NEPP6 compound; 0/NEPP6-biotin; 0/Nerve Growth Factors; 0/Neuroprotective Agents; 0/Prostaglandins; 41598-07-6/Prostaglandin D2; 58-85-5/Biotin; 930-30-3/cyclopentenone

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


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