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

• Published in: Acta pharmacologica Sinica Vol. 34; no. 12; pp. 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: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2013; Nature Publishing Group
• Subjects: 1-Phosphatidylinositol 3-kinase; Animals; Biomedical and Life Sciences; Biomedicine; Carbazoles - pharmacology; ERK; Extracellular Signal-Regulated MAP Kinases - metabolism; GAP-43; Immunology; Internal Medicine; Medical Microbiology; Neurites - drug effects; Neurites - physiology; Original; original-article; PC12 Cells; PC12细胞; Pharmacology/Toxicology; Rats; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - drug effects; Vaccine; Western印迹; 信号通路; 神经生长因子; 轴突生长; 黄皮酰胺; ERK1/2; neurodegenerative disease; Claulansine F; nerve growth factor; GAP-43; PC12 cell; neuritogenesis
• ISSN: 1671-4083; 1745-7254; 1745-7254
• DOI: 10.1038/aps.2013.95

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.