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

作　　者：Yin-zhong MA Na NING Wen-bin HE Jing-wei LI Jin-feng HU Shi-feng CHU Nai-hong CHEN 

机构地区：[1]State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China [2]Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China [3]Shanxi University of Traditional Chinese Medicine, Taiyuan 030024, China

出　　处：《Acta Pharmacologica Sinica》2013年第12期1499-1507,共9页中国药理学报（英文版）

摘　　要：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.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.

关 键 词：Claulansine F PC12 cell NEURITOGENESIS GAP-43 ERK1/2 nerve growth factor neurodegenerative disease 

分 类 号：Q421[生物学—神经生物学] Q426[生物学—生理学]