Claulansine F promotes neuritogenesis in PC12 cells via the ERK signaling pathway

Aim： To study the effects of Claulansine F （Clau F）, a carbazole alkaloid isolated from the stem of Clausena lansium （Lour） Skeels, on neuritogenesis of PC12 cells, and to elucidate the mechanism of action. Methods： Neuritogenesis of PC12 cells was quantified under an inverted microscope. Expression...

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Bibliographic Details
Published in:Acta pharmacologica Sinica 2013-12, Vol.34 (12), p.1499-1507
Main Authors: Ma, Yin-zhong, Ning, Na, He, Wen-bin, Li, Jing-wei, Hu, Jin-feng, Chu, Shi-feng, Chen, Nai-hong
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Animals
Carbazoles - pharmacology
ERK
Extracellular Signal-Regulated MAP Kinases - metabolism
GAP-43
Neurites - drug effects
Neurites - physiology
Original
PC12 Cells
PC12细胞
Rats
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction - drug effects
Western印迹
信号通路
神经生长因子
轴突生长
黄皮酰胺
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Summary:Aim： To study the effects of Claulansine F （Clau F）, a carbazole alkaloid isolated from the stem of Clausena lansium （Lour） Skeels, on neuritogenesis of PC12 cells, and to elucidate the mechanism of action. Methods： Neuritogenesis of PC12 cells was quantified under an inverted microscope. Expression of the neurite outgrowth marker GAP-43 was detected using immunofluorescence. GAP-43 transcription was measured using RT-PCR. Cell viability was evaluated with MTT assay. The levels of phosphor-ERK1/2, phosphor-CREB, phosphor-AKT and acetylate-p53 in the cells were examined using Western blotting analyses. Results： Clau F （10-100 pmol/L） significantly increased the percentage of PC12 cells bearing neurites. Clau F markedly increased the expression of GAP-43 in the cells. The efficiency of Clau F （10 pmol/L） in increasing neuritogenesis and GAP-43 expression was comparable to that of nerve growth factor （50 ng/mL）. In addition, Clau F completely blocked the proliferation of PC12 cells within 7 d of incubation, whereas it did not cause cell death in cultured rat cortical neurons. Treatment of PC12 cells with Clau F activated both ERK and AKT signaling pathways. Co-treatment of PC12 cells with the specific ERK inhibitor PD98059, but not the specific PI3K inhibitor LY294002, blocked Clau F-induced neuritogenesis and GAP-43 upregulation. Conclusion： Clau F promotes neuritogenesis in PC12 cells specifically via activation of the ERK signaling pathway.
ISSN:1671-4083
1745-7254
DOI:10.1038/aps.2013.95