Claulansine F promotes neuritogenesis in PC12 cells via the ERK signaling pathway
Autor: | Jing-Wei Li, Shifeng Chu, Jin-Feng Hu, Wen-bin He, Na Ning, Yin-zhong Ma, Nai-Hong Chen |
---|---|
Rok vydání: | 2013 |
Předmět: |
Pharmacology
MAPK/ERK pathway Neurite Reverse Transcriptase Polymerase Chain Reaction Carbazoles General Medicine Molecular biology PC12 Cells Rats chemistry.chemical_compound Nerve growth factor chemistry Neurites Animals Pharmacology (medical) LY294002 MTT assay Original Article Viability assay Extracellular Signal-Regulated MAP Kinases Protein kinase B PI3K/AKT/mTOR pathway Signal Transduction |
Zdroj: | Acta pharmacologica Sinica. 34(12) |
ISSN: | 1745-7254 |
Popis: | 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. 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. Clau F (10–100 μmol/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 μmol/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. Clau F promotes neuritogenesis in PC12 cells specifically via activation of the ERK signaling pathway. |
Databáze: | OpenAIRE |
Externí odkaz: |