Document Detail

Differences in neuritogenic response to nitric oxide in PC12 and PC12h cells.
MedLine Citation:
PMID:  16239071     Owner:  NLM     Status:  MEDLINE    
We have demonstrated that a natural iridoid compound, genipin, induces neurite outgrowth through the nitric oxide (NO)-cGMP-protein kinase G signaling pathway in PC12h cells. PC12 cells, the parental cell line of PC12h cells, have been shown to carry out neurite extension that accompanies NO production in response to nerve growth factor (NGF). This neurite outgrowth was significantly inhibited by NG-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, in both PC12 and PC12h cells, suggesting that the neuritogenesis is NO-dependent in both cells. In this report, we investigated whether genipin also induces neurite outgrowth in PC12 cells in order to determine the NO-dependent neurotrophic action of genipin in more than just one cell type. Genipin induced marked neurite outgrowth in PC12h cells but not in PC12 cells. The genipin-induced neurite outgrowth was significantly inhibited by L-NAME in PC12h cells. An NO donor, NOR4, also significantly induced neurite outgrowth in a concentration-dependent manner in PC12h cells but not in PC12 cells. On the other hand, NGF-primed PC12 cells exhibited significant neurite extension, which was inhibited by L-NAME, in response to genipin. Interestingly, NGF-primed PC12 cells responded to NOR4 extending neurites and expressed detectable neuronal NO synthase protein which is not detected in naive PC12 cells. These results suggest that genipin exerts a neuritogenic action on neuronal cells which are responsive to NO itself. Furthermore, the results also suggest that PC12h cells are more suitable for the study of NO-dependent neuronal function than PC12 cells which were not responsive to NO.
Matsumi Yamazaki; Kenzo Chiba; Tetsuro Mohri
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-10-18
Journal Detail:
Title:  Neuroscience letters     Volume:  393     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-26     Completed Date:  2006-03-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  222-5     Citation Subset:  IM    
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, HO-3 Kanagawa-machi, Kanazawa, Ishikawa 920-1181, Japan.
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MeSH Terms
Blotting, Western / methods
Cell Differentiation / drug effects*
Dose-Response Relationship, Drug
Drug Interactions
Enzyme Inhibitors / pharmacology
Gene Expression Regulation / drug effects
NG-Nitroarginine Methyl Ester / pharmacology
Nerve Growth Factor / pharmacology
Neurites / drug effects*
Neurons / cytology*,  drug effects
Nitric Oxide / physiology*
PC12 Cells
Pyrans / pharmacology*
Pyridines / pharmacology
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Iridoids; 0/NOR 4; 0/Pyrans; 0/Pyridines; 10102-43-9/Nitric Oxide; 50903-99-6/NG-Nitroarginine Methyl Ester; 6902-77-8/genipin; 9061-61-4/Nerve Growth Factor

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

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