title: Tenuifoliside A promotes neurite outgrowth in PC12 cells via the PI3K/AKT and MEK/ERK/CREB signaling pathways.
abstract: Previous studies have demonstrated the neuroprotective effect of tenuifoliside A (TFSA) on corticosterone-induced neuron damage in SH‑SY5Y cells, however, the effect of TFSA on the promotion of neurite outgrowth remains to be elucidated. PC12 cells were treated with TFSA or nerve growth factor, and the levels of proteins were evaluated by western blotting. In addition, for pharmacological experiments, inhibitors of the PD98059 mitogen‑activated protein kinase kinase (MEK) and phosphatidylinositol 3‑kinase (PI3K; LY294002) were added into the culture medium. The present study demonstrated that TFSA significantly increased the percentage of neurite‑bearing cells and promoted neurite extension in PC12 cells. In addition, TFSA‑treated PC12 cells also expressed increased levels of the 43 kD growth‑associated protein (GAP‑43) neural marker, comparable to those in nerve growth factor‑treated cells. The present study also demonstrated that TFSA enhanced the phosphorylation of extracellular signal‑regulated kinase (ERK) and Akt, which are important signaling molecules involved in neural differentiation in PC12 cells. Co‑treatment of the PC12 cells with the PD98059 MEK inhibitor and LY294002 PI3K inhibitor inhibited the neurite outgrowth induced by TFSA. In addition, treatment with TFSA also promoted the phosphorylation of cyclic AMP response element‑binding protein (CREB), which was inhibited completely by treatment with PD98059. In conclusion, the results of the present study demonstrated that TFSA induces neurite extension of PC12 cells and suggested that activation of the MEK/ERK/CREB and PI3K/Akt signaling pathways is involved in this process.
authors.affiliation: Neurosurgery Unit, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Neurosurgery Unit, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Neurosurgery Unit, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004186:Disaccharidases / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D004186:Disaccharidases; C000589515:tenuifoliside A