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)

Adenosine 3',5'-cyclic monophosphate (cAMP) may be one of the important factors in regulating the expression of many differentiated functions in neuroblastoma cells, but some of these functions can be induced by agents that do not increase the intracellular level of cAMP. An elevation of the intracellular level of guanosine 3',5'-cyclic monophosphate (cGMP) neither induced differentiation nor antagonized the effects of cAMP. Neuroblastoma cells increased the level of cAMP-binding proteins during differentiation, whereas glial cells and L-cells did not. This might have accounted in part for an increase in the intracellular level of cAMP even in the presence of high phosphodiesterase activity in neuroblastoma cells, since the protein-bound with the same proteins, but cAMP had about 10 times higher affinity than did cGMP. cAMP promoted the organization of microtubules and microfilaments necessary for the expression of differentiated phenotypes. The extension of neurites required the synthesis of new protein, but it did not need the synthesis of new RNA. cAMP induced differentiation in neuroblastoma cells by increasing the expression of some genetic information while suppressing the expression of others; e.g., the activities of neural enzymes increased, whereas the synthesis of histone and the phosphorylation of H1-histone markedly decreased in differentiated cells. A hypothesis was offered: An increase in cAMP phosphodiesterase activity as a result of mutation in the regulatory gene for phosphodiesterase in a single, or group of, dividing nerve cell(s) is the primary lesion that leads to malignancy. Based on the concept that selective cytocytoxic drugs should be used with agents that cause differentiation, a new therapeutic approach was suggested for the treatment of neuroblastoma. This involved administration of sodium butyrate followed by L-DOPA or prostaglandin E1 in the presence of cAMP phosphodiesterase inhibitor followed by the less immunosuppressive vincristine and 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide.
 ...
PMID:Cyclic nucleotides in the regulation of expression of differentiated functions in neuroblastoma cells. 1 Apr 49

Exposure of neuroblastoma cells (NBD-2) to 8-bromo-adenosine 3',5'-cyclic monophosphate (0.2-1.0 mM) (8-Br-cAMP) for 15 min caused a long term increase in the Vmax of tyrosine-3-monooxygenase activity (TH) beginning about 1 day after 8-Br-cAMP application. Cyclic AMP-dependent histone kinase was maximally activated in about 30 min and stayed activated above pretreatment levels for one hour. In cells exposed to 8-Br-cAMP for 15 min, separation of soluble and particle bound histone kinase showed that the total histone kinase activity in the soluble fraction decreased by 40%. This decrease was accompanied by an increase in protein kinase activity in the particulate fraction, suggesting enzyme translocation. After translocation, the enzyme appears to acquire a different substrate affinity because it prefers as a PO43- acceptor, acidic protein rather than histone. In NBD-2 cells this kinase appears to precede, and may be related to, the delayed increase in TH Vmax.
 ...
PMID:Translocation of cytosol protein kinase into nuclei and the induction of tyrosine hydroxylase in NBD-2 neuroblastoma cells. 3 81

Chromatin was prepared from isolated nuclei of proliferating and differentiated cultures of C1300 mouse neuroblastoma cells. Differentiation was induced by serum withdrawal or treatment with dibutyryl cyclic AMP. The ability to support DNA-dependent RNA synthesis when assayed in a cell-free system is three times greater for chromatin from proliferating cells. Histones isolated from proliferating and differentiated cells were fractionated electrophoretically. The relative amounts of proteins present in the five major histone fractions were similar. In contrast, there were significant differences in the nonhistone chromosomal proteins synthesized and associated with the genome of proliferating and differentiating neuroblastoma cells. Such differences are reflected by modifications in the electrophoretic banding patterns and in incorporation of [3H]tryptophan into various molecular weight classes of nonhistone chromosomal polypeptides. A functional relationship between changes in the nonhistone chromosomal proteins and variations in the transcriptional activity accompanying differentiation of neuroblastoma cells may exist.
 ...
PMID:Gene expression in mouse neuroblastoma cells: properties of the genome. 105 97

Insulin-like growth factors (IGFs) are implicated in the development of the vertebrate neural circuitry, and increase neurite growth in vitro and in vivo. The construction of the cytoskeleton is necessary for growth of axons and dendrites, and the neurofilament (NF) 68 kDa and 170 kDa proteins assemble to help form major fibrillar elements of the neurite cytoskeleton. We report that physiological concentrations of insulin, IGF-I or IGF-II increased the contents of 68 kDa NF, 170 kDa NF, alpha-tubulin, and beta-tubulin mRNAs, relative to total RNA, in cultured human neuroblastoma SH-SY5Y cells. In contrast, the relative contents of histone 3.3 mRNA, and poly(A)+ RNA were not increased. Ligand concentrations which increased NF mRNAs were very similar to those which increased neurite outgrowth. Although each gene was evidently independently regulated, the 68 kDa NF, 170 kDa NF, alpha-tubulin, and beta-tubulin mRNAs were nevertheless all transiently elevated over approximately the same time interval in response to insulin. These data, when considered together with studies by others with nerve growth factor, show that the 68 kDa and 170 kDa NF mRNAs are elevated in a biochemical pathway activated in common during neurite outgrowth directed by insulin, IGF-I, IGF-II, and nerve growth factor.
 ...
PMID:Effects of insulin and insulin-like growth factors on neurofilament mRNA and tubulin mRNA content in human neuroblastoma SH-SY5Y cells. 132 Jul 19

SH-SY5Y human neuroblastoma cells can be induced to differentiate into a neuronal phenotype by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). In other cell systems, TPA treatment frequently leads to down-regulation of protein kinase C (PKC). However, we now report that TPA-treated and non-treated SH-SY5Y cells express PKC-alpha, but not PKC-beta and PKC-gamma, mRNA. Furthermore, only a slight down-regulation of the PKC-alpha protein could be seen during prolonged treatment with 16 nM TPA, the concentration giving optimal differentiation. In contrast, a higher concentration of TPA (1.6 microM) results in a poor neuronal differentiation and a complete down-regulation of PKC-alpha. PKC-alpha was rapidly translocated to the particulate fraction and remained membrane bound for at least 4 days during treatment with 16 nM TPA. In such cells a sustained increased level of the phosphorylated form of a 80,000 Dalton PKC-substrate was found. In addition to this sustained augmented phosphorylation, administration of fresh TPA at day 4 caused a small but reproducible further increased level of phosphorylated substrate. When the PKC activity was measured by the histone phosphorylation assay a substantial fraction of the initial enzyme activity could still be detected after 4 days of TPA treatment. Taken together, the data demonstrate that PKC remains functionally active during TPA induced differentiation of SH-SY5Y cells, which may suggest a continuous role for the enzyme during the differentiation process.
 ...
PMID:Protein kinase C remains functionally active during TPA induced neuronal differentiation of SH-SY5Y human neuroblastoma cells. 150 12

Histone H1t has been purified from rat testes and antibodies were elicited in rabbits. Immunoblotting studies with anti-histone H1t-IgG have shown that it reacted specifically with histone H1t but not with other histone H1 subtypes, namely H1a, -b, -c, -d, -e and H10. The anti-histone H1t-IgG also did not react with chicken erythrocyte histone H5. Immunoblotting studies have also revealed that the polyclonal anti-histone H1t-IgG reacted with (a) two polypeptide fragments, NBS-N and NBS-C, derived from N-bromosuccinimide cleavage of histone H1t, (b) two polypeptide fragments, CT-N and CT-C, derived from alpha-chymotrypsin cleavage of histone H1t, and (c) GH1t, globular domain of histone H1t obtained after trypsin cleavage. The indirect immunofluorescence studies on nuclei isolated from adult rat testes with anti-histone H1t-IgG showed that the fluorescence, particularly, of the pachytene nucleus was the brightest. On the other hand, anti-histone H1t-IgG did not stain nuclei from either liver or nuclei isolated from the testes of 10-day-old rats.
 ...
PMID:Testis-specific histone H1t is antigenically distinct among H1 subtypes. 241 27

Neurotrophic factors may increase axon and dendrite growth in part by regulating the content of cytoskeletal elements such as microtubules, which are comprised of tubulin subunits. The mechanism by which insulin, insulin-like growth factors (IGFs), and nerve growth factor (NGF) can increase the relative abundance of tubulin mRNAs as a prelude to neurite formation was studied. Insulin significantly increased the abundance of tubulin mRNAs relative to total RNA in cultured human neuroblastoma SH-SY5Y cells. This increase was not the result of a generalized elevation of all transcripts, because tubulin mRNAs were elevated relative to poly(A)+ RNA as well. Moreover, whereas polymerases I and III were elevated in activity, polymerase II was not. Tubulin mRNAs were stabilized against degradation in the presence of actinomycin D by both insulin and IGF-I. In contrast, actin and histone 3.3 mRNAs were neither increased nor stabilized. Insulin did not alter alpha- or beta-tubulin gene transcription rates in nuclear run-off experiments, and did increase the relative synthesis of tubulin proteins. These results suggest that tubulin mRNA levels are increased mainly through selective stabilization by insulin and IGFs. Because NGF is known to stabilize tubulin mRNA levels also, stabilization of tubulin mRNAs is suggested to be a common event in the pathway leading to neurite elongation directed by neuritogenic polypeptides.
 ...
PMID:Stabilization of tubulin mRNAs by insulin and insulin-like growth factor I during neurite formation. 269 75

We have compared the effects of forskolin, N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (dibutyryl cyclic AMP, Bt2-cAMP), and butyrate on several aspects of neuroblastoma cell physiology. The morphology of Neuro 2A cells was similar after incubation with forskolin and Bt2-cAMP, which caused extensive neurite outgrowth, whereas in the presence of butyrate some rudimentary neurites were formed but they were not nearly as extensive. All compounds produced a dose-dependent inhibition of cell proliferation, but the effect of Bt2-cAMP was more marked than that caused by forskolin, thus showing that the effect of Bt2-cAMP is due partially to the butyrate released. Acetylcholinesterase activity was lower in the cells incubated with butyrate or Bt2-cAMP than in untreated cells or in forskolin-treated cells. This suggests that cyclic AMP does not play a role in the regulation of this enzyme. Bt2-cAMP produced histone acetylation, a well-known effect of butyrate in cultured cells, whereas forskolin did not affect this modification. Consequently, the levels of thyroid hormone receptor, a nuclear protein whose concentration is regulated by butyrate through changes in acetylation of chromatin proteins, were decreased in cells incubated with Bt2-cAMP or butyrate, but were unaffected by forskolin. Butyrate elevated the concentration of histone H1(0), a protein that increases in neuroblastoma cells as a result of different treatments that block cell division. The concentration of H1(0) in the cells treated with Bt2-cAMP was at a level intermediate between that found after treatment with butyrate and with forskolin. The present results clearly indicate that some of the effects of Bt2-cAMP on neuroblastoma cells can be attributed to the butyryl moiety of this compound rather than to the cyclic nucleotide itself.
 ...
PMID:Comparison of the effects of forskolin and dibutyryl cyclic AMP in neuroblastoma cells: evidence that some of the actions of dibutyryl cyclic AMP are mediated by butyrate. 284 86

The accumulation of histone H1o in mouse NIE-115 neuroblastoma cells was measured during the course of three treatments that block cell division. Over the course of 12 days, these treatments, 5 mM butyrate, 2% dimethyl sulfoxide, and serum withdrawal, all resulted in decreased levels of DNA synthesis and increased levels of H1o (in absolute terms and relative to the other H1 histones, H1abc). However, the increase in H1o differed comparing butyrate treatment, where there was a 6-fold increase in the H1o/H1abc ratio, with the other two treatments which both had only 3-fold increases in the H1o/H1abc ratio. The mechanism for increasing H1o differed for each of the three treatments and involved differential changes in both synthesis and degradation of the H1 subfractions to favor H1o accumulation on the chromatin. Despite the obvious correlation of the increase in H1o levels with the inhibition of DNA replication, we also showed that increases in H1o can occur without any change in DNA synthesis when cells are switched from media containing dimethyl sulfoxide to media with butyrate as the blocking agent. Finally, there was no correlation between the production of neurites in this cell line and H1o accumulation, arguing against simple, direct involvement of H1o in differentiation.
 ...
PMID:Mechanisms of H1o accumulation in mouse neuroblastoma cells differ with different treatments. 308 78

The nuclear protein kinase NI (NI kinase) was purified from NB-15 mouse neuroblastoma cells by phosphocellulose column and casein affinity column chromatography. The purified NI kinase exhibited (i) an apparent subunit molecular weight of about 37,000, (ii) autophosphorylation, and (iii) insensitivity to inhibition by heparin. When NI kinase was added to heat-treated neuroblastoma nuclei in the presence of [gamma-32P] ATP, two proteins with apparent subunit molecular weights of 11,000 and 10,000 were prominently phosphorylated. Other protein kinases tested including the nuclear protein kinase NII, Type I cAMP-dependent protein kinase, and protein kinase C did not catalyze the phosphorylation of these two proteins. The NI kinase-catalyzed phosphorylation of these two proteins was completely inhibited by 1 mM spermine. In contrast, 10 mM putrescine, 2 mM spermidine, 5 mM arginine, and 10 mM NH4Cl, had no inhibitory effect on this phosphorylation reaction. Our study also indicated that the phosphorylation of the 11,000- and 10,000-dalton proteins occurred in the nuclear matrix fraction but not in heterogeneous nuclear ribonucleoproteins, high mobility group proteins, or histone fractions. We have previously reported that spermine specifically inhibits the endogenous phosphorylation of an 11,000-dalton nuclear protein in various mammalian cell lines (Chen, K. Y., and Verma, R. (1984) Biochem. Biophys. Res. Commun. 118, 710-716). The present study suggests that the 11,000- and 10,000-dalton nuclear proteins may be native substrates of nuclear protein kinase NI and that their phosphorylation can be affected by physiological concentrations of spermine.
 ...
PMID:Spermine inhibits the phosphorylation of the 11,000- and 10,000-dalton nuclear proteins catalyzed by nuclear protein kinase NI in NB-15 mouse neuroblastoma cells. 394 52


1 2 3 4 5 6 7 8 9 10 Next >>