Document Detail

Induction of PC12 cell differentiation by flavonoids is dependent upon extracellular signal-regulated kinase activation.
MedLine Citation:
PMID:  15312169     Owner:  NLM     Status:  MEDLINE    
Many of the physiological benefits attributed to flavonoids are thought to stem from their potent antioxidant and free radical scavenging properties. Recently, it was shown that flavonoids protect nerve cells from oxidative stress by multiple mechanisms, only one of which is directly related to their antioxidant activity, suggesting that specific flavonoids may have other properties that could make them useful in the treatment of conditions that lead to nerve cell death. In particular, it was asked if any flavonoid could mimic neurotrophic proteins. To examine this possibility, we looked at the ability of flavonoids to induce nerve cell differentiation using PC12 cells. PC12 cells were treated with a variety of flavonoids to determine if there was a correlation between their neuroprotective activity and their neurite outgrowth-promoting activity. In addition, the signaling pathways required for flavonoid-induced differentiation were examined. We found that only a small subset of the flavonoids that were neuroprotective could induce neurite outgrowth by an extracellular signal-regulated kinase-dependent process. There was a strong correlation between the concentrations of the flavonoids that were neuroprotective and the concentrations that induced differentiation. These results suggest that the consumption of specific flavonoids could have further beneficial effects on nerve cells following injury, in pathological conditions or in normal aging.
Yutaka Sagara; Julie Vanhnasy; Pamela Maher
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  90     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-17     Completed Date:  2004-09-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1144-55     Citation Subset:  IM    
Copyright Information:
Copyright 2004 International Society for Neurochemistry
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
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MeSH Terms
Acetylcysteine / pharmacology
Ascorbic Acid / pharmacology
Blotting, Western / methods
Cell Differentiation / drug effects*
Dose-Response Relationship, Drug
Drug Interactions
Enzyme Activation
Enzyme Inhibitors / pharmacology
Flavonoids / pharmacology*
Free Radical Scavengers / pharmacology
GTP Phosphohydrolases / metabolism
Mitogen-Activated Protein Kinases / metabolism*,  physiology
Nerve Growth Factor / pharmacology
PC12 Cells
Phosphorylation / drug effects
Time Factors
ras Proteins / metabolism
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Flavonoids; 0/Free Radical Scavengers; 50-81-7/Ascorbic Acid; 528-48-3/fisetin; 616-91-1/Acetylcysteine; 9061-61-4/Nerve Growth Factor; EC Protein Kinases; EC 3.6.1.-/GTP Phosphohydrolases; EC Proteins

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