Clivorine, an otonecine pyrrolizidine alkaloid from Ligularia species, impairs neuronal differentiation via NGF-induced signaling pathway in cultured PC12 cells
| Autor: | Gallant K.L. Chan, Li Yang, Kelly Y.C. Lam, Huangquan Lin, Karl Wah Keung Tsim, Zhengtao Wang, Kitty K.M. Lau, Cathy W. C. Bi, Artemis Lu Yan, Aizhen Xiong, Tina T. X. Dong |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Neurite Cell Survival Cellular differentiation Pharmaceutical Science Biology Asteraceae PC12 Cells 03 medical and health sciences Drug Discovery Nerve Growth Factor Animals MTT assay Viability assay Phosphorylation Receptor trkA Protein kinase B Pyrrolizidine Alkaloids Pharmacology Neurons Dose-Response Relationship Drug Cell growth Cell Differentiation Molecular biology Rats Oncogene Protein v-akt 030104 developmental biology Nerve growth factor nervous system Complementary and alternative medicine Molecular Medicine Signal transduction Signal Transduction |
| Zdroj: | Phytomedicine : international journal of phytotherapy and phytopharmacology. 23(9) |
| ISSN: | 1618-095X |
| Popis: | Pyrrolizidine alkaloids (PAs) are commonly found in many plants including those used in medical therapeutics. The hepatotoxicities of PAs have been demonstrated both in vivo and in vitro; however, the neurotoxicities of PAs are rarely mentioned.In this study, we aimed to investigate in vitro neurotoxicities of clivorine, one of the PAs found in various Ligularia species, in cultured PC12 cells.PC12 cell line was employed to first elucidate the neurotoxicity and the underlying mechanism of clivorine, including cell viability and morphology change, neuronal differentiation marker and signaling pathway.PC12 cells were challenged with series concentrations of clivorine and/or nerve growth factor (NGF). The cell lysates were collected for MTT assay, trypan blue staining, immunocytofluorescent staining, qRT-PCR and western blotting.Clivorine inhibited cell proliferation and neuronal differentiation evidenced by MTT assay and dose-dependently reducing neurite outgrowth, respectively. In addition, clivorine decreased the level of mRNAs encoding for neuronal differentiation markers, e.g. neurofilaments and TrkA (NGF receptor). Furthermore, clivorine reduced the NGF-induced the phosphorylations of TrkA, protein kinase B and cAMP response element-binding protein in cultured PC12 cells.Taken together, our results suggest that clivorine might possess neurotoxicities in PC12 cells via down-regulating the NGF/TrkA/Akt signaling pathway. PAs not only damage the liver, but also possess neurotoxicities, which could possibly result in brain disorders, such as depression. |
| Databáze: | OpenAIRE |
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