Journal
ACTA PHARMACOLOGICA SINICA
Volume 34, Issue 12, Pages 1499-1507Publisher
ACTA PHARMACOLOGICA SINICA
DOI: 10.1038/aps.2013.95
Keywords
Claulansine F; PC12 cell; neuritogenesis; GAP-43; ERK1/2; nerve growth factor; neurodegenerative disease
Funding
- National Natural Science Foundation of China [81274122, 81273629, 81001487]
- Special Purpose for New Drug Development [2012ZX09301002-004]
- Studies on the Structure and Function of Bioactive Substances from Natural Medicines [IRT1007]
- Beijing Natural Science Foundation [7131013]
- Research Fund for the Doctoral Program of Higher Education of China [20121106130001]
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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 mu mol/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 mu mol/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.
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