scholarly journals Neurite Outgrowth in PC12 Cells Stimulated by Components fromDendranthema×grandiflorumcv. “Mottenohoka” Is Enhanced by Suppressing Phosphorylation of p38MAPK

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Atsuyoshi Nishina ◽  
Hirokazu Kimura ◽  
Hiroyuki Tsukagoshi ◽  
Kunihisa Kozawa ◽  
Mamoru Koketsu ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Active Components ◽  
Extracellular Signal Regulated Kinase ◽  
Promote Neurite Outgrowth ◽  
Extracellular Signal ◽  
Enhance Neurite Outgrowth

Components fromDendranthema×grandiflorumcv. “Mottenohoka” that promote neurite outgrowth of PC12 cells were identified and the mechanism of neurite outgrowth stimulated by isolated components was studied. Components that promoted the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2) of PC12 cells were isolated. From various structural analyses, the active components were identified as acacetin and luteolin. The effects of acacetin or luteolin on PC12 cells were evaluated by electro-blotting and immunostaining. Slight neurite outgrowth in PC12 cells was observed within 2 days of culture after stimulation by luteolin or acacetin. However, NGF-stimulation induced remarkable neurite outgrowth in comparison. Neurite outgrowth by luteolin or acacetin was significantly enhanced by pretreatment with SB203580 (a p38MAPK inhibitor). The results of this study into the phosphorylation of ERK 1/2 and p38MAPK by flavonoids suggest that the inhibition of p38MAPK phosphorylation may effectively enhance neurite outgrowth.

scholarly journals Bioactivity-Guided Fractionation Identifies Amygdalin as a Potent Neurotrophic Agent from Herbal MedicineSemen PersicaeExtract

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Chuanbin Yang ◽  
Jia Zhao ◽  
Yuanyuan Cheng ◽  
Xuechen Li ◽  
Jianhui Rong
Keyword(s):  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Blood Stasis ◽  
Reverse Phase Hplc ◽  
Extracellular Signal Regulated Kinase ◽  
Neurotrophic Activity ◽  
Liquid Liquid Extraction ◽  
Fractionation Procedure ◽  
Extracellular Signal

Herbal medicineSemen Persicaeis widely used to treat blood stasis in Chinese medicine and other oriental folk medicines. Although little is known about the effects ofSemen Persicaeand its active compounds on neuron differentiation, our pilot study showed thatSemen Persicaeextract promoted neurite outgrowth in rat dopaminergic PC12 cells. In the present study, we developed a bioactivity-guided fractionation procedure for the characterization of the neurotrophic activity ofSemen Persicaeextract. The resultant fractions were assayed for neurite outgrowth in PC12 cells based on microscopic assessment. Through liquid-liquid extraction and reverse phase HPLC separation, a botanical glycoside amygdalin was isolated as the active compound responsible for the neurotrophic activity ofSemen Persicaeextract. Moreover, we found that amygdalin rapidly induced the activation of extracellular-signal-regulated kinase 1/2 (ERK1/2). A specific ERK1/2 inhibitor PD98059 attenuated the stimulatory effect of amygdalin on neurite outgrowth. Taken together, amygdalin was identified as a potent neurotrophic agent fromSemen Persicaeextract through a bioactivity-guided fractional procedure. The neurotrophic activity of amygdalin may be mediated by the activation of ERK1/2 pathway.

scholarly journals The Insulin Receptor: A Potential Target of Amarogentin Isolated from Gentiana rigescens Franch That Induces Neurogenesis in PC12 Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 581
Author(s):  
Lihong Cheng ◽  
Hiroyuki Osada ◽  
Tianyan Xing ◽  
Minoru Yoshida ◽  
Lan Xiang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Insulin Receptor ◽  
Signaling Pathways ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Mitogen Activated Protein Kinase ◽  
Potential Target ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Gentiana Rigescens

Amarogentin (AMA) is a secoiridoid glycoside isolated from the traditional Chinese medicine, Gentiana rigescens Franch. AMA exhibits nerve growth factor (NGF)-mimicking and NGF-enhancing activities in PC12 cells and in primary cortical neuron cells. In this study, a possible mechanism was found showing the remarkable induction of phosphorylation of the insulin receptor (INSR) and protein kinase B (AKT). The potential target of AMA was predicted by using a small-interfering RNA (siRNA) and the cellular thermal shift assay (CETSA). The AMA-induced neurite outgrowth was reduced by the siRNA against the INSR and the results of the CETSA suggested that the INSR showed a significant thermal stability-shifted effect upon AMA treatment. Other neurotrophic signaling pathways in PC12 cells were investigated using specific inhibitors, Western blotting and PC12(rasN17) and PC12(mtGAP) mutants. The inhibitors of the glucocorticoid receptor (GR), phospholipase C (PLC) and protein kinase C (PKC), Ras, Raf and mitogen-activated protein kinase (MEK) significantly reduced the neurite outgrowth induced by AMA in PC12 cells. Furthermore, the phosphorylation reactions of GR, PLC, PKC and an extracellular signal-regulated kinase (ERK) were significantly increased after inducing AMA and markedly decreased after treatment with the corresponding inhibitors. Collectively, these results suggested that AMA-induced neuritogenic activity in PC12 cells potentially depended on targeting the INSR and activating the downstream Ras/Raf/ERK and PI3K/AKT signaling pathways. In addition, the GR/PLC/PKC signaling pathway was found to be involved in the neurogenesis effect of AMA.

scholarly journals Stimulation of neurite outgrowth in PC12 cells by EGF and KCl depolarization: a Ca(2+)-independent phenomenon.

1995 ◽  
Vol 130 (3) ◽  
pp. 701-710 ◽  
Author(s):  
M D Mark ◽  
Y Liu ◽  
S T Wong ◽  
T R Hinds ◽  
D R Storm
Keyword(s):  
Map Kinase ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Kinase Activity ◽  
Neurite Growth ◽  
Intracellular Camp ◽  
Regulation Of Transcription ◽  
Promote Neurite Outgrowth ◽  
Synergistic Regulation ◽  
Stimulation Of

MAP kinase activity is necessary for growth factor induction of neurite outgrowth in PC12 cells. Although NGF and EGF both stimulate MAP kinase activity, EGF does not stimulate neurite extension. We report that EGF, in combination with KCl, stimulates neurite outgrowth in PC12 cells. This phenomenon was independent of intracellular Ca2+ increases and not due to enhancement of MAP kinase activity over that seen with EGF alone. However, EGF plus KCl increased intracellular cAMP, and other cAMP elevating agents acted synergistically with EGF to promote neurite outgrowth. Stimulation of neurite outgrowth by cAMP and EGF was blocked by inhibitors of transcription suggesting that synergistic regulation of transcription by the cAMP and MAP kinase pathways may stimulate neurite growth.

scholarly journals Role of Phosphoinositide 3-Kinase and Endocytosis in Nerve Growth Factor-Induced Extracellular Signal-Regulated Kinase Activation via Ras and Rap1

2000 ◽  
Vol 20 (21) ◽  
pp. 8069-8083 ◽  
Author(s):  
Randall D. York ◽  
Derek C. Molliver ◽  
Savraj S. Grewal ◽  
Paula E. Stenberg ◽  
Edwin W. McCleskey ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Map Kinase ◽  
Pc12 Cells ◽  
Erk Signaling ◽  
Nerve Growth ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Phosphoinositide 3 Kinase

ABSTRACT Neurotrophins promote multiple actions on neuronal cells including cell survival and differentiation. The best-studied neurotrophin, nerve growth factor (NGF), is a major survival factor in sympathetic and sensory neurons and promotes differentiation in a well-studied model system, PC12 cells. To mediate these actions, NGF binds to the TrkA receptor to trigger intracellular signaling cascades. Two kinases whose activities mediate these processes include the mitogen-activated protein (MAP) kinase (or extracellular signal-regulated kinase [ERK]) and phosphoinositide 3-kinase (PI3-K). To examine potential interactions between the ERK and PI3-K pathways, we studied the requirement of PI3-K for NGF activation of the ERK signaling cascade in dorsal root ganglion cells and PC12 cells. We show that PI3-K is required for TrkA internalization and participates in NGF signaling to ERKs via distinct actions on the small G proteins Ras and Rap1. In PC12 cells, NGF activates Ras and Rap1 to elicit the rapid and sustained activation of ERKs respectively. We show here that Rap1 activation requires both TrkA internalization and PI3-K, whereas Ras activation requires neither TrkA internalization nor PI3-K. Both inhibitors of PI3-K and inhibitors of endocytosis prevent GTP loading of Rap1 and block sustained ERK activation by NGF. PI3-K and endocytosis may also regulate ERK signaling at a second site downstream of Ras, since both rapid ERK activation and the Ras-dependent activation of the MAP kinase kinase kinase B-Raf are blocked by inhibition of either PI3-K or endocytosis. The results of this study suggest that PI3-K may be required for the signals initiated by TrkA internalization and demonstrate that specific endocytic events may distinguish ERK signaling via Rap1 and Ras.

scholarly journals Calcium influx into neurons can solely account for cell contact-dependent neurite outgrowth stimulated by transfected L1.

1992 ◽  
Vol 119 (4) ◽  
pp. 883-892 ◽  
Author(s):  
E J Williams ◽  
P Doherty ◽  
G Turner ◽  
R A Reid ◽  
J J Hemperly ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Calcium Influx ◽  
Polysialic Acid ◽  
Cell Contact ◽  
3T3 Cells ◽  
Cerebellar Neurons ◽  
Calcium Dependent ◽  
Promote Neurite Outgrowth ◽  
Neural Cell Adhesion

We have used monolayers of control 3T3 cells and 3T3 cells expressing transfected human L1 as a culture substrate for rat PC12 cells and rat cerebellar neurons. PC12 cells and cerebellar neurons extended longer neurites on human L1 expressing cells. Neurons isolated from the cerebellum at postnatal day 9 responded equally as well as those isolated at postnatal day 1-4, and this contrasts with the failure of these older neurons to respond to the transfected human neural cell adhesion molecule (NCAM). Human L1-dependent neurite outgrowth could be blocked by antibodies that bound to rat L1 and, additionally, the response could be fully inhibited by pertussis toxin and substantially inhibited by antagonists of L- and N-type calcium channels. Calcium influx into neurons induced by K+ depolarization fully mimics the L1 response. Furthermore, we show that L1- and K+(-)dependent neurite outgrowth can be specifically inhibited by a reduction in extracellular calcium to 0.25 microM, and by pretreatment of cerebellar neurons with the intracellular calcium chelator BAPTA/AM. In contrast, the response was not inhibited by heparin or by removal of polysialic acid from neuronal NCAM both of which substantially inhibit NCAM-dependent neurite outgrowth. These data demonstrate that whereas NCAM and L1 promote neurite outgrowth via activation of a common CAM-specific second messenger pathway in neurons, neuronal responsiveness to NCAM and L1 is not coordinately regulated via posttranslational processing of NCAM. The fact that NCAM- and L1-dependent neurite outgrowth, but not adhesion, are calcium dependent provides further evidence that adhesion per se does not directly contribute to neurite outgrowth.

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