Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthetic undecameric peptide, pGlu-Pro-Pro-Gly-Gly-Ser-Lys-Val-Ile-Leu-Phe, known as the hydra head activator peptide, present in high concentrations in mammalian hypothalamus and intestine, was tested for neurotrophic activity in a survival assay using cultured chick embryonic sympathetic and dorsal root ganglion cells, and for morphological differentiation activity on neuroblastoma cells. Hydra head activator peptide supported neuron survival. The optimal active concentration, 1 pM, was very similar to the concentration that causes bud and head formation in hydra. Maximal neuron survival obtained with hydra head activator peptide was close to that obtained with nerve growth factor: both substances enhanced survival up to 3 times that of control cultures. Bradykinin, which has some amino acid sequence homology with hydra head activator, was inactive as a neurotrophic factor. Hydra head activator induced rapid morphological differentiation of the mouse neuroblastoma cell line Neuro-2A. Neuro-2A responded to the peptide by process extension, 4 h after its addition to the culture medium. Neurotrophic factors isolated to date have been characterized by their ability to maintain cell viability and enhance neurite outgrowth. Hydra head activator peptide met these two criteria when tested in 3 different neuron culture systems. Our results suggest that the head activator peptide may act as a neurotrophic factor for neurons in other species, including mammals.
 ...
PMID:Hydra head activator peptide has trophic activity for eukaryotic neurons. 152 28

Alzheimer's disease is characterized by the loss of cholinergic neurons in the nucleus basalis of Meynert and by a primary loss of memory function. Since staurosporine has been reported to induce differentiation in human neuroblastoma cells in vitro, we studied the effects of staurosporine on the amnesia induced by basal forebrain-lesion in rats. Staurosporine (0.05 and 0.1 mg/kg intraperitoneal) attenuated the impaired performance of water maze and passive avoidance tasks, even though the drug administration began 2 weeks after the lesion. Moreover, staurosporine (0.1 mg/kg) partially reversed the decrease of choline acetyltransferase activity in the fronto-parietal cortex induced by basal forebrain-lesion. These results suggest that staurosporine attenuates impairment of learning through reversal of damage to cholinergic neurons induced by basal forebrain-lesion. This evidence indicates that neurotrophic factor-like substances may be used in novel therapeutic approaches to Alzheimer's disease.
 ...
PMID:Staurosporine facilitates recovery from the basal forebrain-lesion-induced impairment of learning and deficit of cholinergic neuron in rats. 203 5

We have investigated whether administration of staurosporine, which has been reported to induce differentiation in the human neuroblastoma cell in vitro, attenuates amnesia induced by basal forebrain lesion in rats. Multiple dosage of staurosporine at the doses of 0.05 and 0.1 mg/kg (i.p.) attenuated the impaired performance of the water maze task. Moreover, staurosporine (0.1 mg/kg) reversed the decrease of choline acetyltransferase activity in the fronto-parietal cortex. These results suggest that staurosporine attenuates amnesia through reversal of deficits in cholinergic neurons induced by basal forebrain lesion, and that neurotrophic factor-like substances may open the way for novel therapeutic approaches to Alzheimer's disease.
 ...
PMID:Staurosporine, a protein kinase inhibitor, attenuates basal forebrain-lesion-induced amnesia and cholinergic neuronal deficit. 205 30

Until recently, nerve growth factor could be considered the only neurotrophic factor with an established physiological role. We discuss the emerging evidence indicating that the insulinlike factors may constitute a family of related neurotrophic proteins, and the observations suggesting that the receptor for the phorbol ester tumor promoters is closely associated with neuronal differentiation. The emphasis of the discussion is placed on neurite formation under multiple modulation by insulinlike factors, nerve growth factor, and tumor promoter receptors in sensory, sympathetic and human neuroblastoma cells.
 ...
PMID:Neurite formation modulated by nerve growth factor, insulin, and tumor promoter receptors. 298 43

Retinoic acid (RA), the acid form of vitamin A, is shown to enhance the synthesis of nerve growth factor (NGF) in cultures of mouse L cells. Maximal stimulation was observed in cells growing in a serum-free medium supplemented with 10(-6)M RA during 48 h. The drug increased both the level of NGF mRNA and the amount of mature NGF protein secreted by the cells. RA was previously reported to increase the number of NGF receptors on some neuroblastoma cells (Haskell et al., 1987 Cell and Tiss. Res., 247, 67-73). It seems, therefore, that RA may influence nerve cell differentiation by promoting both the synthesis of the neurotrophic factor and the responsiveness of target cells.
 ...
PMID:Retinoic acid increases the expression of NGF gene in mouse L cells. 342 88

We investigated the effect of neurotrophic factors on dopamine (DA) cells in vitro. At concentrations of nanograms/c.c. basic fibroblast growth factor (bFGF) is a more potent DA-trophic agent than brain derived neurotrophic factor (BDNF) or epidermal growth factor (EGF) in fetal mid brain neurons. In these cells, bFGF produces a greater increase of DA levels and percentage of cells positive for tyrosine hydroxylase (TH+) than BDNF and EGF. Acidic fibroblast growth factor (aFGF) was not tested in fetal DA cells since aFGF requires heparin for its effect and fetal mid brain cultures do not grow well in the presence of a high concentration of heparin. We further investigated the effect of bFGF and aFGF, and two of their analogs, in catecholamine rich human neuroblastoma cells NB69. In these cells aFGF, at concentrations of picograms/c.c., increases DA levels, while its analogs, E118 and super short, have no effect. Acidic FGF also increases norepinephrine levels, the number of TH+ cells, and the percentage of TH+ with respect to the total number of nuclei. Basic fibroblast growth factor (bFGF) produced similar, but less potent effects. Acidic FGF was active only in the presence of heparin; the effect of bFGF was independent of heparin. FGFs are promising drugs for the treatment of PD, though further investigations with these compounds should be performed before their use in clinical trials.
 ...
PMID:Fibroblast growth factors: structure-activity on dopamine neurons in vitro. 760 86

Prosaposin, recently identified as a neurotrophic factor (1), is the precursor of saposins A, B, C, and D. The neurotrophic activity of prosaposin resides in the saposin C domain. We have pinpointed the active sequence to a linear 12-mer located in the NH2-terminal sequence of saposin C (LIDNNKTEKEIL). Nanomolar concentrations of a 22-mer peptide encompassing this region stimulated neurite outgrowth and choline acetyltransferase activity, and prevented cell death in neuroblastoma cells. In primary cerebellar granule cells, the 22-mer also stimulated neurite outgroth. Studies of the neuroblastoma line NS20Y using a radiolabeled 18-mer from the neurotrophic region identified a high-affinity (Kd = 70 pM) binding site indicative of receptor-ligand interaction. The 22-mer stimulated protein phosphorylation of several proteins, some of which were tyrosine-phosphorylated after brief exposure similar to saposin C. Circular dichroism studies demonstrated that the 22-mer was converted from a random to a helical structure by addition of ganglioside GM1. The results are consistent with receptor-ligand binding by the peptide initiating a signal transduction cascade and resulting in neuronal differentiation.
 ...
PMID:Identification of the neurotrophic factor sequence of prosaposin. 776 61

The protein kinase inhibitor K-252a has been shown to promote cholinergic activity in cultures of rat spinal cord and neuronal survival in chick dorsal root ganglion cultures. To determine the mechanism by which K-252a acts as a neurotrophic factor, we examined the effects of this molecule on a human neuroblastoma cell line, SH-SY5Y. K-252a induced neurite outgrowth in a dose-dependent manner. Coincident with neurite outgrowth was the early tyrosine phosphorylation of 125- and 140-kDa proteins. The phosphorylation events were independent of protein kinase C inhibition because down-regulation of protein kinase C by long-term treatment with phorbol ester did not prevent K252a-induced tyrosine phosphorylation. Similarly, the protein kinase C inhibitors H7, GF-109203X, and calphostin C did not induce the phosphorylation. We have identified one of the phosphosubstrates as the pp125 focal adhesion protein tyrosine kinase (Fak). Induction of phosphorylation coincided with increased Fak activity and appeared to be independent of ligand/integrin interaction. The induction of Fak phosphorylation by K-252a was also observed in LA-N-5 cells and primary cultures of rat embryonic striatal cells but not in PC12 cells. The protein kinase C-independent induction of tyrosine phosphorylation and the identification of Fak as a substrate of K-252a-induced tyrosine kinase activity suggest that this compound mediates neurotrophic effects through a novel signaling pathway.
 ...
PMID:K-252a induces tyrosine phosphorylation of the focal adhesion kinase and neurite outgrowth in human neuroblastoma SH-SY5Y cells. 783 46

Prosaposin was identified as a neurotrophic factor stimulating neurite outgrowth in murine neuroblastoma (NS20Y) cells and choline acetyltransferase (ChAT) activity in human neuroblastoma (SK-N-MC) cells. The four naturally occurring saposins, which are derived by proteolytic processing of prosaposin, were tested for activity. Saposin C was found to be active, whereas saposins A, B, and D were inactive as neurotrophic factors. Dose-response curves demonstrated that nanomolar concentrations of prosaposin and saposin C stimulated neurite outgrowth and increased ChAT activity. Prosaposin and saposin C exerted activity by a mechanism independent of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3. Binding assays utilizing saposin C as a ligand gave two saturable binding constants, a high-affinity (Kd = 19 pM) and a low-affinity (Kd = 1 nM) constant, with 2000 and 15,000 sites per NS20Y cell, respectively. Phosphorylation stimulation experiments demonstrated that brief treatment with prosaposin or saposin C enhanced phosphorylation of a variety of proteins, some of which contained phosphorylated tyrosine(s). Since both cell lines were also stimulated by ciliary neurotrophic factor (CNTF) as well as prosaposin, inhibition was tested by utilizing an anti-gp130 monoclonal antibody, which specifically inhibited CNTF stimulation; this antibody did not inhibit prosaposin or saposin C stimulation. These results indicate that prosaposin and saposin C are neurotrophic factors which initiate signal transduction by binding to a high-affinity receptor that induces protein phosphorylation.
 ...
PMID:Identification of prosaposin as a neurotrophic factor. 793 12

The C6 glial cell line has been used as a model cell system for the investigation of new glial produced neurotrophic and neurotropic molecules. By using the C6 cell line grown in a defined medium on collagen, this laboratory has isolated a distinct neurite promoting factor (NPF) that is potentiated by the presence of collagen (CPNPF). We have observed that C6 cells cultured in a defined medium on collagen (rat type-I) slowed their growth rate and expressed an astrocytic- or oligodendrocytic-like morphology. CPNPF, at this state of purity, appears to be a distinct NPF which induces neurite outgrowth (neurites of 1 or more somal diameters) in PC12 cells. These neurite promotion effects, however, appear to support the neuron morphology for only a short period (4 days) of time without the presence of neurotrophic factor (NTF). The neurite promoting activity is ineffective in inducing neurite outgrowth using mouse neuroblastoma cells (neuro-2a). CPNPF appears to be a heat stable protein whose activity does not depend on the presence of intact collagen, heparin sulfate proteoglycan (HSPG), or chondroitin sulfate proteoglycan (CSPG). Exposure to dissociative conditions results in a loss of neurite promoting activity. CPNPF is not a glycoprotein that contains an accessible alpha-D-mannopyranosyl, alpha-D-glucopyranosyl, or a sterically related residue (hydroxyl groups in the C-3,4, and 5 positions). Although these residues are not present on all glycoproteins, it does indicate that CPNPF is most likely not a glycoprotein. CPNPF activity is not blocked by neutralizing antibodies directed toward NGF, beta-FGF, IL-1 beta, IL-6, TGF-beta 2, TGF-beta 1.2, TGF-beta 3, TGF-beta 5, or EGF. CPNPF appears to either be oligomeric protein or a complex of proteins. On the basis of indirect evidence, it does not appear to be glial derived protease nexin-I. The alteration in morphology of the C6 glial cell line by serum-free conditions in the presence of collagen may have induced the production of a potentially new NPF not seen by previous investigators.
 ...
PMID:Identification of a collagen potentiated neurite promoting factor isolated from C6 glioma cells. 836 Sep 47


1 2 3 4 5 6 7 Next >>