Sea urchin gangliosides exhibit neuritogenic effects in neuronal PC12 cells via TrkA- and TrkB-related pathways

2021 ◽  
Vol 85 (3) ◽  
pp. 675-686
Author(s):  
Xiaoxu Wang ◽  
Yiyang Li ◽  
Yuliu Wang ◽  
Yanjun Liu ◽  
Changhu Xue ◽  
...  
Keyword(s):  
Nervous System ◽  
Nerve Growth Factor ◽  
Pc12 Cells ◽  
Sea Urchin ◽  
Neurotrophic Factors ◽  
Tyrosine Kinase Receptors ◽  
Neuronal Pc12 Cells ◽  
Dose Dependent ◽  
Specific Inhibitors

ABSTRACT Gangliosides (GLSs) are ubiquitously distributed in all tissues but highly enriched in nervous system. Currently, it is unclear how exogenous GLSs regulate neuritogenesis, although neural functions of endogenous GLSs are widely studied. Herein, we evaluated the neuritogenic activities and mechanism of sea urchin gangliosides (SU-GLSs) in vitro. These different glycosylated SU-GLSs, including GM4(1S), GD4(1S), GD4(2A), and GD4(2G), promoted differentiation of NGF-induced PC12 cells in a dose-dependent and structure-selective manner. Sulfate-type and disialo-type GLSs exhibited stronger neuritogenic effects than monosialoganglioside GM1. Furthermore, SU-GLSs might act as neurotrophic factors possessing neuritogenic effects, via targeting tyrosine-kinase receptors (TrkA and TrkB) and activating MEK1/2-ERK1/2-CREB and PI3K-Akt-CREB pathways. This activation resulted in increased expression and secretion of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). These pathways were verified by specific inhibitors. Our results confirmed the neuritogenic functions of SU-GLS in vitro and indicated their potential roles as natural nutrition for neuritogenesis.

scholarly journals Nerve growth factor withdrawal-induced cell death in neuronal PC12 cells resembles that in sympathetic neurons.

1992 ◽  
Vol 119 (6) ◽  
pp. 1669-1680 ◽  
Author(s):  
P W Mesner ◽  
T R Winters ◽  
S H Green
Keyword(s):  
Cell Death ◽  
Protein Synthesis ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Programmed Cell Death ◽  
Pc12 Cells ◽  
Sympathetic Neurons ◽  
Nerve Growth ◽  
Neuronal Pc12 Cells ◽  
New Protein

Previous studies have shown that in neuronal cells the developmental phenomenon of programmed cell death is an active process, requiring synthesis of both RNA and protein. This presumably reflects a requirement for novel gene products to effect cell death. It is shown here that the death of nerve growth factor-deprived neuronal PC12 cells occurs at the same rate as that of rat sympathetic neurons and, like rat sympathetic neurons, involves new transcription and translation. In nerve growth factor-deprived neuronal PC12 cells, a decline in metabolic activity, assessed by uptake of [3H]2-deoxyglucose, precedes the decline in cell number, assessed by counts of trypan blue-excluding cells. Both declines are prevented by actinomycin D and anisomycin. In contrast, the death of nonneuronal (chromaffin-like) PC12 cells is not inhibited by transcription or translation inhibitors and thus does not require new protein synthesis. DNA fragmentation by internucleosomal cleavage does not appear to be a consistent or significant aspect of cell death in sympathetic neurons, neuronal PC12 cells, or nonneuronal PC12 cells, notwithstanding that the putative nuclease inhibitor aurintricarboxylic acid protects sympathetic neurons, as well as neuronal and nonneuronal PC12 cells, from death induced by trophic factor removal. Both phenotypic classes of PC12 cells respond to aurintricarboxylic acid with similar dose-response characteristics. Our results indicate that programmed cell death in neuronal PC12 cells, but not in nonneuronal PC12 cells, resembles programmed cell death in sympathetic neurons in significant mechanistic aspects: time course, role of new protein synthesis, and lack of a significant degree of DNA fragmentation.

Vasoinhibin Suppresses Nerve Growth Factor-Induced Differentiation and Survival of PC12 Pheochromocytoma Cells

2019 ◽  
Vol 109 (2) ◽  
pp. 152-164 ◽  
Author(s):  
Zesergio Melo ◽  
Ximena Castillo ◽  
Bibiana Moreno-Carranza ◽  
María G. Ledesma-Colunga ◽  
Edith Arnold ◽  
...  
Keyword(s):  
Nervous System ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cell Survival ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Dna Fragmentation ◽  
Lentiviral Vector ◽  
Induced Differentiation ◽  
Pheochromocytoma Cells

Background: Vasoinhibin, a protein derived from prolactin, regulates various vascular functions including endothelial cell survival. Of note, vasoinhibin is present in the central nervous system, where it triggers neuroendocrine and behavioral responses to stress. Moreover, vasoinhibin compromises nerve growth factor (NGF)-induced neurite outgrowth in primary sensory neurons of the peripheral nervous system. Nonetheless, information on the functions of vasoinhibin in developing neurons remains limited. The present study explored whether vasoinhibin affects the neurotrophic actions of NGF by measuring the cell differentiation and survival of PC12 pheochromocytoma cells. Methods: The effects of recombinant or lentiviral vector-transduced human vasoinhibin were tested on differentiating PC12 cells. Neurite outgrowth was quantified by measuring their length and density. The MTT assay was employed to assess cell viability, and ELISA was used to quantify DNA fragmentation as an index of apoptosis. Phosphorylated Akt and ERK1/2 were analyzed by Western blotting. Results: The addition of a human recombinant vasoinhibin, and the transduction of a lentiviral vector carrying a human vasoinhibin sequence, significantly reduced NGF-induced neurite outgrowth, cell survival, and phosphorylation of Akt and ERK1/2, and increased DNA fragmentation and caspase 3 activation in PC12 cells. Conclusions: Vasoinhibin downregulates NGF-induced differentiation and survival of PC12 cells, blocking tropomyosin receptor kinase A-triggered signaling pathways and increasing apoptosis. These results establish that vasoinhibin interaction with NGF and other neurotrophins may be critical in mediating pathways involved in neuronal survival and differentiation.

scholarly journals Dose-Dependent Differential Effect of Neurotrophic Factors on In Vitro and In Vivo Regeneration of Motor and Sensory Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Daniel Santos ◽  
Francisco Gonzalez-Perez ◽  
Xavier Navarro ◽  
Jaume del Valle
Keyword(s):  
Neurite Outgrowth ◽  
Functional Recovery ◽  
Neurotrophic Factors ◽  
Collagen Matrix ◽  
High Dose ◽  
Organotypic Cultures ◽  
High Doses ◽  
Dose Dependent

Although peripheral axons can regenerate after nerve transection and repair, functional recovery is usually poor due to inaccurate reinnervation. Neurotrophic factors promote directional guidance to regenerating axons and their selective application may help to improve functional recovery. Hence, we have characterized in organotypic cultures of spinal cord and dorsal root ganglia the effect of GDNF, FGF-2, NGF, NT-3, and BDNF at different concentrations on motor and sensory neurite outgrowth. In vitro results show that GDNF and FGF-2 enhanced both motor and sensory neurite outgrowth, NGF and NT-3 were the most selective to enhance sensory neurite outgrowth, and high doses of BDNF selectively enhanced motor neurite outgrowth. Then, NGF, NT-3, and BDNF (as the most selective factors) were delivered in a collagen matrix within a silicone tube to repair the severed sciatic nerve of rats. Quantification of Fluorogold retrolabeled neurons showed that NGF and NT-3 did not show preferential effect on sensory regeneration whereas BDNF preferentially promoted motor axons regeneration. Therefore, the selective effects of NGF and NT-3 shown in vitro are lost when they are applied in vivo, but a high dose of BDNF is able to selectively enhance motor neuron regeneration both in vitro and in vivo.

MiR-203 Involves in Neuropathic Pain Development and Represses Rap1a Expression in Nerve Growth Factor Differentiated Neuronal PC12 Cells

2015 ◽  
Vol 31 (1) ◽  
pp. 36-43 ◽  
Author(s):  
Haixia Li ◽  
Yuguang Huang ◽  
Chao Ma ◽  
Xuerong Yu ◽  
Zhiyong Zhang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Nerve Growth ◽  
Neuronal Pc12 Cells

scholarly journals Nerve growth factor-induced neurite outgrowth in PC12 cells involves the coordinate induction of microtubule assembly and assembly-promoting factors.

1985 ◽  
Vol 101 (5) ◽  
pp. 1799-1807 ◽  
Author(s):  
D G Drubin ◽  
S C Feinstein ◽  
E M Shooter ◽  
M W Kirschner
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Time Course ◽  
Microtubule Assembly ◽  
Nerve Growth ◽  
Peripheral Neurons ◽  
Associated Proteins

Nerve growth factor (NGF) regulates the microtubule-dependent extension and maintenance of axons by some peripheral neurons. We show here that one effect of NGF is to promote microtubule assembly during neurite outgrowth in PC12 cells. Though NGF causes an increase in total tubulin levels, the formation of neurites and the assembly of microtubules follow a time course completely distinct from that of the tubulin induction. The increases in microtubule mass and neurite extension closely parallel 10- and 20-fold inductions of tau and MAP1, proteins shown previously to promote microtubule assembly in vitro. When NGF is removed from PC12 cells, neurites disappear, microtubule mass decreases, and both microtubule-associated proteins return to undifferentiated levels. These data suggest that the induction of tau and MAP1 in response to NGF promotes microtubule assembly and that these factors are therefore key regulators of neurite outgrowth.

Studies on some aspects of the rôle of sulfhydryl groups in morphogenesis

Development ◽  
1965 ◽  
Vol 14 (2) ◽  
pp. 129-135
Author(s):  
Leela Mulherkar ◽  
K. Vasudeva Rao ◽  
S. Sanjivani Joshi
Keyword(s):  
Nervous System ◽  
Ethyl Alcohol ◽  
Present Report ◽  
Sulfhydryl Groups ◽  
Sh Groups ◽  
Stage Of Development ◽  
Sulfhydryl Compounds ◽  
Specific Inhibitors

The importance of sulfhydryl compounds in the process of morphogenesis was pointed out by Brachet (1950). Using specific inhibitors of -SH such as chloroacetophenone, it has been shown that embryos develop a number of malformations when the activity of -SH groups is interfered with (Beatty, 1951; Deuchar, 1957; Lakshmi, 1962a). It has been observed that the abnormalities are mainly in the nervous system and these findings are in agreement with the distribution of -SH groups in embryos of amphibia (Brachet, 1950) and chick (Rulon, 1935). These studies have vindicated the importance of -SH containing proteins stressed by Brachet. In the present report are described some studies using chloroacetophenone (CAP) as an -SH inhibitor and cysteine to reverse its action. Fresh fertilized hen's eggs were incubated to obtain the desired stage of development and explanted in vitro by the method described by New (1955). A stock solution of 0·01 M ο-chloroacetophenone (BDH) was prepared in 50 per cent. ethyl alcohol.

Nerve growth factor inhibits apoptosis induced by S-100 binding in neuronal PC12 cells

Neuroscience ◽  
1996 ◽  
Vol 76 (1) ◽  
pp. 159-166 ◽  
Author(s):  
S Fulle ◽  
M.A Mariggiò ◽  
S Belia ◽  
I Nicoletti ◽  
G Fanò
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Nerve Growth ◽  
S 100 ◽  
Neuronal Pc12 Cells
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