Tenuifoliside A promotes neurite outgrowth in PC12 cells via the PI3K/AKT and MEK/ERK/CREB signaling pathways

Abstract

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.

Graphene Oxide–Silver Nanoparticles Nanocomposite Stimulates Differentiation in Human Neuroblastoma Cancer Cells (SH-SY5Y)

“…Among the tested nanomaterials, GO-AgNPs strongly promoted the expression of all tested genes, which is due to the two different unique physical and chemical properties of nanomaterials in the single platform and working synergistically. Our findings gained support from a previous study suggesting that AgNPs could induce neuronal differentiation via modulation of ROS, phosphatases, and kinase signaling pathways such as Akt and Erk1/2 in SH-SY5Y cells and oligosaccharide esters of tenuifoliside A promotes neurite outgrowth in PC12 cells via activation of various signaling pathways including mitogen-activated protein kinase kinase (MEK),extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate (cAMP) response element binding (CREB) and Phosphatidylinositol-3-Kinase and Protein Kinase B (PI3K/Akt) [ 14 , 69 ]. Tetramethylpyrazine (TMP) induces differentiation in SH-SY5Y cells by expression of ERK1/2 and PI3K/Akt by modulating TopoIIβ expression [ 70 ].…”

Vasoinhibin Suppresses the Neurotrophic Effects of VEGF and NGF in Newborn Rat Primary Sensory Neurons

“…The effects of both VEGF and NGF on neuritogenesis have been shown to involve activation of the ERK and AKT pathways [38][39][40][41]. ERK and AKT are critical signaling molecules mediating many cellular processes including proliferation, differentiation, development, survival, and apoptosis [42,43].…”

Genomic Control of Upregulation of GRP78 Expression for Promotion of Neurite Elongation and Attenuation of Cell Death via PKA-Mediated Signaling in PC12 Cells

“…PC12 cell is a developmental model neuron to study neurite extension system and formation of neuron-like networks through intracellular signaling pathway(s) [14]. Then, we discover that fsk-mediated PKA signaling upregulates GRP78 to bear neurites via an effect on the GRP78 promoter region by using PC12 cells.…”