Inhibition of Nerve Growth Factor-Induced Neurite Outgrowth from PC12 Cells by Dexamethasone: Signaling Pathways through the Glucocorticoid Receptor and Phosphorylated Akt and ERK1/2

Terada, Kazuki; Kojima, Yoshitsugu; Watanabe, Takayuki; Izumo, Nobuo; Chiba, Koji; Karube, Yoshiharu

doi:10.1371/journal.pone.0093223

Cited by 35 publications

(20 citation statements)

References 37 publications

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“…These results also indicated that Erk and Akt work cooperatively to promote neurite outgrowth induced by TJ24 and TJ68. Thus, it seems likely that the kampo medicines promoted neurite outgrowth via activation of both the ERK1/2 and Akt pathways [17]. Indeed, we found further evidence that phosphorylation of both ERK1/2 and Akt is increased, in correlation with our other findings (Fig.…”

Section: Discussionsupporting

confidence: 91%

Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells

Konaka

Moriyama

Sakurada

et al. 2017

J Pharm Health Care Sci

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BackgroundIn chemotherapy, the full round of treatment must be completed as scheduled to achieve the strongest therapeutic effect. However, peripheral neuropathy, a severe side effect of the chemotherapeutic agent paclitaxel, can force the premature discontinuation of treatment. As some kampo practitioners have suggested that it may be possible to counteract such side effects, we analyzed the effects of Kamishoyosan, Shakuyakukanzoto, and Goshajinkigan in an in vitro model of paclitaxel-induced peripheral neuropathy.MethodsPaclitaxel-treated PC12 cells were assessed for neurite length and performed Western blot analysis for growth-associated protein-43 (GAP-43) and light neurofilament protein (NF-L) levels in the presence of nerve growth factor (NGF); they were re-assessed, with additional testing for acetylcholinesterase levels, after application of one of the kampo. We also compared phosphorylation of extracellular signal-regulated kinase (Erk)1/2 and Akt via Western blot analysis. About effect of kampo to anticancer efficacy, we confirmed cell cytotoxicity in A549 cells using MTT assay.ResultsAddition of Kamishoyosan or Shakuyakukanzoto, but not Goshajinkigan, significantly improved neurite length and GAP-43 and NF-L levels from paclitaxel-treated PC12 cells, relative to those of only NGF-treated PC12 cells. The promoting effect of Kamishoyosan and Shakuyakukanzoto in neurite outgrowth is confirmed when NGF promoted neurite outgrowth, and it was inhibited partially when Erk1/2 and Akt were blocked by Erk1/2 inhibitor or Akt inhibitor alone. Furthermore, neurite outgrowth induced by TJ24 and TJ68 was inhibited more strongly when Erk1/2 inhibitor and Akt inhibitor were treated at the same time. NGF with Kamishoyosan or Shakuyakukanzoto promoted the proportion of phosphorylated Erk1/2 and phosphorylated Akt compare with NGF only. On the other hand, Kamishoyosan or Shakuyakukanzoto didn’t influence cytotoxicity of paclitaxel in A549 cells.ConclusionsKamishoyosan or Shakuyakukanzoto promotes neurite outgrowth with NGF via increasing the proportion of phosphorylated Erk1/2 and phosphorylated Akt in PC12 cells. The effect applies to recovery from paclitaxel-induced axonal involvement and might promote recovery from paclitaxel-induced neuropathy without influence of anticancer effect of paclitaxel.

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Section: Discussionsupporting

confidence: 91%

Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells

Konaka

Moriyama

Sakurada

et al. 2017

J Pharm Health Care Sci

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“…The neurite outgrowth of PC12 cells was measured following the method described by Terada et al [30,34]. PC12 cells were seeded into type I collagen-coated 60-mm tissue culture dishes (Iwaki, Tokyo, Japan) at a density of 1.5 × 10 5 cells/dish in DMEM/F-12 containing 10% FBS for 24 h. After incubation, PC12 cells were stimulated with differentiation medium (DMEM/F-12 containing 5% FBS plus 50 ng/mL NGF with or without either Riv at 0.1–100 μM, Phy at 100 μM, or Sig-1R agonist PRE-084 and Sig-2R agonist PB28 at 10 μM).…”

Section: Methodsmentioning

confidence: 99%

Cholinesterase inhibitor rivastigmine enhances nerve growth factor-induced neurite outgrowth in PC12 cells via sigma-1 and sigma-2 receptors

et al. 2018

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Rivastigmine (Riv) is a potent and selective cholinesterase (acetylcholinesterase, AChE and butyrylcholinesterase, BuChE) inhibitor developed for the treatment of Alzheimer’s disease (AD). To elucidate whether Riv causes neuronal differentiation, we examined its effect on nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. At concentrations of 0–100 μM, Riv was non-toxic in PC12 cells. Riv caused dose-dependent (10–100 μM) enhancement of NGF-induced neurite outgrowth, which was completely inhibited by the TrkA antagonist GW-441756. By contrast, Riv-mediated enhancement of neurite outgrowth was not blocked by the acetylcholine receptor antagonists, scopolamine and hexamethonium. However, the sigma-1 receptor (Sig-1R) antagonist NE-100 and sigma-2 receptor (Sig-2R) antagonist SM-21 each blocked about half of the Riv-mediated enhancement of NGF-induced neurite outgrowth. Interestingly, the simultaneous application of NE-100 and SM-21 completely blocked the enhancement of NGF-induced neurite outgrowth by Riv. These findings suggest that both Sig-1R and Sig-2R play important roles in NGF-induced neurite outgrowth through TrkA and that Riv may contribute to neuronal repair via Sig-1R and Sig-2R in AD therapy.

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“…bFGF has previously been reported to activate MEK/ERK pathways and consequently induce neuronal differentiation in rat pheochromocytoma cells (PC12), mouse or human neuroblastoma cell lines (Neuro2A, SK-N-SH and BE(2)-C), and embryonic stem cells [ 2 , 3 , 5 , 7 , 46 ]. In mouse BMSCs, a MEK/ERK inhibitor attenuated bFGF-induced neuronal differentiation, but a PI3K inhibitor failed to induce the bFGF effect [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor Receptor-2 Contributes to the Basic Fibroblast Growth Factor-Induced Neuronal Differentiation in Canine Bone Marrow Stromal Cells via Phosphoinositide 3-Kinase/Akt Signaling Pathway

et al. 2015

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Bone marrow stromal cells (BMSCs) are considered as candidates for regenerative therapy and a useful model for studying neuronal differentiation. The role of basic fibroblast growth factor (bFGF) in neuronal differentiation has been previously studied; however, the signaling pathway involved in this process remains poorly understood. In this study, we investigated the signaling pathway in the bFGF-induced neuronal differentiation of canine BMSCs. bFGF induced the mRNA expression of the neuron marker, microtubule associated protein-2 (MAP2) and the neuron-like morphological change in canine BMSCs. In the presence of inhibitors of fibroblast growth factor receptors (FGFR), phosphatidylinositol 3-kinase (PI3K) and Akt, i.e., SU5402, LY294002, and MK2206, respectively, bFGF failed to induce the MAP2 mRNA expression and the neuron-like morphological change. bFGF induced Akt phosphorylation, but it was attenuated by the FGFR inhibitor SU5402 and the PI3K inhibitor LY294002. In canine BMSCs, expression of FGFR-1 and FGFR-2 was confirmed, but only FGFR-2 activation was detected by cross-linking and immunoprecipitation analysis. Small interfering RNA-mediated knockdown of FGFR-2 in canine BMSCs resulted in the attenuation of bFGF-induced Akt phosphorylation. These results suggest that the FGFR-2/PI3K/Akt signaling pathway is involved in the bFGF-induced neuronal differentiation of canine BMSCs.

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Inhibition of Nerve Growth Factor-Induced Neurite Outgrowth from PC12 Cells by Dexamethasone: Signaling Pathways through the Glucocorticoid Receptor and Phosphorylated Akt and ERK1/2

Cited by 35 publications

References 37 publications

Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells

Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells

Cholinesterase inhibitor rivastigmine enhances nerve growth factor-induced neurite outgrowth in PC12 cells via sigma-1 and sigma-2 receptors

Fibroblast Growth Factor Receptor-2 Contributes to the Basic Fibroblast Growth Factor-Induced Neuronal Differentiation in Canine Bone Marrow Stromal Cells via Phosphoinositide 3-Kinase/Akt Signaling Pathway

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