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)

Lithium ion entry at low concentrations (1 to 5 mM) into an electrically active adrenergic clone of mouse neuroblastoma cells was stimulated by veratridine; and this stimulation was blocked by tetrodotoxin, These data provide biochemical evidence that lithium ions enter by way of the sodium channel which may be a major pathway for entry of this ion into electrically active cells.
 ...
PMID:Lithium ion entry through the sodium channel of cultured mouse neuroblastoma cells: a biochemical study. 86 Jan 26

Lithium ion efflux by murine neuroblastoma (clone N1E-115) and rat glioma (clone C6) cells was studied to determine the presence of a phloretin-sensitive sodium-lithium countertransport pathway which has been found in human erythrocytes. Although this pathway could be identified in these cultured cells, unlike that in red blood cells, it was a very minor (less than 20%) component of the overall efflux of lithium ions from these cells of nervous tissue origin.
 ...
PMID:Sodium-dependent lithium ion efflux from murine neuroblastoma and rat glioma cells: a minor pathway for efflux of lithium ions. 642 Aug 27

Serum concentrations of lithium after i.p. administration to normal mice declined with biphasic kinetics. Treatment of mice bearing ascitic L1210 leukemia with lithium resulted in a modest protection against the myelosuppressive effects of vinblastine. Lithium as a single agent was without effect on the survival times of mice bearing either the L1210 or P388 leukemia. Similarly, there was no evidence of significant antiproliferative or cytotoxic activity when cultured L1210 leukemia and murine neuroblastoma cells were exposed to lithium at levels comparable to those observed in the serum of lithium-treated mice. The therapeutic activity of vinblastine against the L1210 and P388 leukemias was not significantly altered by either simultaneous or subsequent administration of lithium. Lithium did not antagonize the antiproliferative or cytotoxic action of vinblastine against L1210 leukemia or murine neuroblastoma cells and was without effect in experiments with neuroblastoma cells that assessed vinblastine inhibition of a biological function dependent on formation of cytoplasmic microtubules (neurite formation induced by serum deprivation). The results obtained suggest that administration of lithium to reduce myelosuppression is not likely to counteract the tumoricidal activity of vinblastine.
 ...
PMID:Effect of lithium on the myelosuppressive and chemotherapeutic activities of vinblastine. 745 46

Lithium has a biphasic effect of the agonist-dependent accumulation of Ins(1,4,5)P3 in human neuroblastoma SH-SY5Y cells. These effects consist of a transient reduction, followed by a long-lasting increase in Ins(1,4,5)P3 as compared to controls. The Li+ effects are dose dependent, and were observed at concentrations used in the treatment of bipolar disorders, and thus may have therapeutic implications. The mechanism of the Li+ effect on Ins(1,4,5)P3 accumulation requires further investigation. The transient reduction of Ins(1,4,5)P3 was observed under conditions where Li+ causes only a moderate increase in the inositol mono- and bi-phosphates. Supplementation with exogenous inositol had no effect on the level of Ins(1,4,5)P3, indicating that the mechanism of the Li(+)-dependent reduction of Ins(1,4,5)P3 is not due to inositol depletion. Li+ did not interfere with degradation of Ins(1,4,5)P3 after receptor-blockage with atropine, suggesting that Li+ has no direct effect on the Ins(1,4,5)P3 metabolizing enzymes. A direct effect of Li+ on the phospholipase C is also unlikely. Entry of Ca2+ into the cells is an important factor, which affects agonist-stimulated accumulation of Ins(1,4,5)P3, as well as absolute values of Li(+)-dependent increase in Ins(1,4,5)P3; however, it is not essential for the manifestation of Li+ effects. Our results also show that manifestation of Li+ effects in human neuroblastoma cells requires the stimulation of muscarinic receptors and activation of PLCs, PKCs, and/or that other staurosporine/H-7/GF 109203X-sensitive protein kinases are involved in the regulation of Ins(1,4,5)P3 during the plateau phase of ACh-stimulation. We also suggest an important role for these enzymes in the Li(+)-dependent elevation of Ins(1,4,5)P3.
 ...
PMID:Phosphoinositide signalling in human neuroblastoma cells: biphasic effect of Li+ on the level of the inositolphosphate second messengers. 886 50

Lithium, a simple monovalent cation, is the mainstay in the treatment of manic-depressive illness, but despite extensive research, its mechanism of action remains to be elucidated. Because lithium requires chronic administration for therapeutic efficacy and because its beneficial effects last well beyond its discontinuation, it has been postulated that lithium may exert major effects at the genomic level. We have previously shown that lithium, at therapeutically relevant concentrations, increases gene expression through the activator protein-1 (AP-1) transcription factor pathway in vitro. In the present study, we have sought to determine if lithium also increases the expression of endogenous genes known to be regulated by AP-1 and have therefore investigated the effects of lithium on tyrosine hydroxylase (TH) levels. Male Wistar rats were treated with LiCl for 9 days (subacute) or 4 weeks (chronic), and TH levels were measured in frontal cortex, hippocampus, and striatum using immunoblotting. Chronic (but not subacute) lithium treatment resulted in significant increases in TH levels in rat frontal cortex, hippocampus, and striatum. Lithium (1 mM) also increased TH levels in human SH-SY5Y neuroblastoma cells in vitro, indicating that lithium increases TH levels in both rodent and human tissues, likely via a direct cellular effect. These effects are compatible with (but likely not exclusively due to) an effect on the DNA binding of the 12-O-tetradecanoylphorbol 13-acetate response element to the AP-1 family of transcription factors.
 ...
PMID:Lithium increases tyrosine hydroxylase levels both in vivo and in vitro. 952 97

The purpose of this study was to examine the modulation of tau phosphorylation mediated by protein kinase A, a kinase with low intrinsic activity, and by the constitutively active glycogen synthase kinase, as well as to examine the subsequent effects on tau-microtubule association in differentiated human SH-SY5Y neuroblastoma cells. Activation of protein kinase A with forskolin and rolipram significantly increased tau phosphorylation at Ser262/356 only in the presence of okadaic acid, indicating that phosphates at these sites are normally turned over rapidly. In contrast, glycogen synthase kinase appears to maintain tau phosphorylation at Thr181 and Ser396/404 since inhibition of glycogen synthase kinase with lithium reduced phosphorylation at these sites. Lithium treatment also significantly decreased tau and tyrosinated alpha-tubulin levels. Perturbation of microtubules with nocodazole or taxol induced tau dephosphorylation at Tau-1 sites, Thr181 and Ser396/404, indicating that both constitutive kinase activity and microtubule state modulate tau phosphorylation at these sites. Nocodazole- or taxol-induced tau dephosphorylation was blocked by the protein phosphatase 2A/1 inhibitor okadaic acid, but not by the protein phosphatase 2B inhibitor cyclosporin A. In addition, osmotic stress, such as treatment with 20 mM NaCl, selectively increased tau phosphorylation at the Tau-1 epitope. To investigate the effect of phosphorylation on tau association with microtubules and microtubule stability in situ, a Triton X-100 extraction assay was utilized to separate the detergent-soluble cytosolic components from the detergent-insoluble cytoskeletal components. In control cells or cells treated with lithium very little tau was detected in the cytosolic fraction. Activation of protein kinase A in the presence of okadaic acid elevated tau levels in the detergent-soluble fraction, which contained all the tau phosphorylated at Ser262/356, and also decreased microtubule stability, as indicated by decreased acetylated alpha-tubulin levels. In conclusion, the phosphorylation state of tau in differentiated SH-SY5Y cells is regulated by glycogen synthase kinase, microtubule dynamics and osmotic stress at overlapping sites which apparently have little influence on tau-microtubule association. In contrast, phosphorylation of tau at Ser262/356 within the microtubule-binding, which was mediated in part by protein kinase A, prevented the association of tau with microtubules in situ.
 ...
PMID:The interrelationship between selective tau phosphorylation and microtubule association. 966 18

Lithium and sodium valproate (VPA) are effective in the treatment of bipolar disorder (BD) and may function through the regulation of signal transduction pathways and transcription factors such as c-fos and c-Jun, which in turn results to changes in gene expression. The long-term efficacy of lithium and VPA in BD suggests that the regulation of gene expression may be an important target for these drugs. Preliminary evidence suggests that c-fos levels and AP-1 binding may be regulated by lithium and VPA, but the results are inconclusive. In the present study, we report differential effects of the two most commonly prescribed mood stabilizers used to treat BD on Fos/Jun protein levels and their AP-1 binding activity in human neuroblastoma SH-SY5Y cells. At therapeutically relevant concentrations, both drugs acutely (<24 h) induced c-Fos immunoreactivity and AP-1 binding. In contrast to lithium, chronic (1 week) treatment with VPA led to continued induction of c-Fos, in addition to induction of c-Jun immunoreactivity and a 33-35 kDa band previously identified as chronic FRA. AP-1 DNA binding activity was also increased after 1 week VPA treatment. These findings suggest that both these mood stabilizers may have an effect on neuronal gene expression of target genes containing the AP-1 consensus sequence in their promoter regions after acute treatment. The present results confirm and extend previous findings on the regulation of c-fos expression and AP-1 binding after administration of mood stabilizers, and further elucidate the mechanisms through which VPA increases AP-1 DNA binding.
 ...
PMID:Differential effects of mood stabilizers on Fos/Jun proteins and AP-1 DNA binding activity in human neuroblastoma SH-SY5Y cells. 968 95

Lithium has been used clinically in the treatment of manic depression. However, its pharmacologic mode of action remains unclear. Characteristics of Li+ interactions in red blood cells (RBCs) have been identified. We investigated Li+ interactions on human neuroblastoma SH-SY5Y cells by developing a novel 7Li NMR method that provided a clear estimation of the intra- and extracellular amounts of Li+ in the presence of the shift reagent thulium-1,4,7,10-tetrazacyclododecane-N,N',N'',N'''-tetramethylene phosphonate (HTmDOTP4-). The first-order rate constants of Li+ influx and efflux for perfused, agarose-embedded SH-SY5Y cells in the presence of 3 mM HTmDOTP4- were 0.055 +/- 0.006 (n = 4) and -0.025 +/- 0.006 min(-1) (n = 3), respectively. Significant increases in the rate constants of Li+ influx and efflux in the presence of 0.05 mM veratridine indicated the presence of Na+ channel-mediated Li+ transport in SH-SY5Y cells. 7Li NMR relaxation measurements showed that Li+ is immobilized more in human neuroblastoma SH-SY5Y cells than in human RBCs.
 ...
PMID:7Li nuclear magnetic resonance study for the determination of Li+ properties in neuroblastoma SH-SY5Y cells. 975 Dec 2

Lithium has neuroprotective effects in a number of model systems which may contribute to the therapeutic effects of lithium in mood disorders. Because the tumor suppressor p53 is linked to cell death, we tested whether lithium administration to human neuroblastoma SH-SY5Y cells modulated the activation of p53. After treatment of cells with H7 (25, 50, and 75 microM), nuclear p53 levels were increased to 464, 816 and 1079% of basal levels, respectively. A 24 h pretreatment with 5 mM lithium reduced these increases by 69, 61 and 28%, respectively. Pretreatment with 2 mM lithium for 1 or 14 days reduced the 25 microM H7-induced elevations of nuclear p53 by 40 and 70%, respectively, and even a 14-day pretreatment with 1 mM lithium caused a significant 16% reduction. Since increased nuclear p53 is a critical intermediate step in many signaling processes that culminate in cell death, attenuation of p53 activation by lithium reveals a mechanism by which lithium may support neuronal survival.
 ...
PMID:Lithium attenuates p53 levels in human neuroblastoma SH-SY5Y cells. 1032 95

Lithium, carbamazepine and sodium valproate are mood stabilizers used in the treatment of bipolar disorder, and although their mechanisms of action remain unknown, signal transduction systems and the associated modulation of gene expression may constitute significant actions. We examined if acute or chronic treatments with these agents modulated the activation of the AP-1 transcription factor or the increased intracellular calcium levels in human neuroblastoma SH-SY5Y cells caused by stimulation with carbachol. AP-1 activation stimulated by carbachol was reduced by pretreatment for 1 h, 24 h or 7 days with 1 mM lithium by 15%, 37%, and 60%, respectively, and with 0.05 mM carbamazepine by 3%, 21%, and 46%, respectively, but not by pretreatment with 0.5 mM sodium valproate. AP-1 DNA binding activity stimulated by carbachol or by phorbol ester-induced activation of protein kinase C was inhibited by the protein kinase C inhibitor Ro31-8220, but phorbol ester-stimulated AP-1 activation was unaltered by 7-day pretreatments with lithium or carbamazepine. Activation of AP-1 by carbachol was dependent on calcium, as it was inhibited by treatment with the extracellular calcium chelator EGTA, the intracellular calcium chelator BAPTA-AM, and the calcium/calmodulin kinase II inhibitor KN62. Pretreatment for 7 days with lithium or carbamazepine had no significant effect on carbachol-stimulated increases in intracellular calcium levels, but reduced the stimulation of AP-1 by the calcium ionophore ionomycin by 30% to 40%. Thus, chronic treatment with the antibipolar agents lithium and carbamazepine attenuates carbachol-stimulated AP-1 DNA binding activity, and these agents preferentially inhibit signaling cascades activated by the calcium rather than the protein kinase C arm of the phosphoinositide signaling pathway.
 ...
PMID:Modulation of carbachol-stimulated AP-1 DNA binding activity by therapeutic agents for bipolar disorder in human neuroblastoma SH-SY5Y cells. 1052 72


1 2 3 Next >>