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)

In these studies we examined the effect of polyol accumulation on neural cell myo-inositol metabolism and properties. Neuroblastoma cells were cultured for two weeks in media containing 30 mM glucose, fructose, galactose or mannose with or without 0.4 mM sorbinil or 250 microM myo-inositol. Chronic exposure of neuroblastoma cells to media containing 30 mM glucose, galactose, or mannose caused a decrease in myo- inositol content and myo-[2-3H]inositol accumulation and incorporation into phosphoinositides compared to cells cultured in unsupplemented medium or medium containing 30 mM fructose as an osmotic control. These monosaccharides each caused an increase in intracellular polyol levels with galactitol > sorbitol = mannitol accumulation. Chronic exposure of neuroblastoma cells to media containing 30 mM glucose, galactose, or mannose caused a significant decrease in Na+/K+ ATPase transport activity, resting membrane potential, and bradykinin-stimulated 32P incorporation into phosphatidylinositol compared to cells cultured in medium containing 30 mM fructose. In contrast, basal incorporation of 32P into phosphatidylinositol or basal and bradykinin-stimulated 32P incorporation into phosphatidylinositol 4,5-bisphosphate were not effected. Each of these cellular functions as well as myo-inositol metabolism and content and polyol levels remained near control values when 0.4 mM sorbinil, an aldose reductase inhibitor, was added to the glucose, galactose, or mannose supplemented media. myo-Inositol metabolism and content and bradykinin-stimulated phosphatidylinositol synthesis were also maintained when media containing 30 mM glucose, galactose, or mannose was supplemented with 250 microM myo-inositol. The results suggest that polyol accumulation induces defects in neural cell myo-inositol metabolism and certain cell functions which could, if they occurred in vivo, contribute to the pathological defects observed in diabetic neuropathy.
 ...
PMID:Reduced Na+/K+ ATPase transport activity, resting membrane potential, and bradykinin-stimulated phosphatidylinositol synthesis by polyol accumulation in cultured neuroblastoma cells. 817 72

myo-Inositol accumulation and incorporation into phosphoinositides was decreased in neuroblastoma cells chronically exposed to medium containing 30 mmol/L glucose or 30 mmol/L galactose. In addition, the intracellular content of myo-inositol and phosphatidylinositol was decreased and the sorbitol or galactitol content increased in cells cultured for 2 weeks in medium containing 30 mmol/L glucose or 30 mmol/L galactose, respectively. Na+/K+ adenosine triphosphatase (ATPase) transport activity was also significantly decreased by long-term exposure of neuroblastoma cells to medium containing 30 mmol/L glucose or 30 mmol/L galactose. When glucose-conditioned cells were placed in medium containing a normal glucose concentration for 24 hours, myo-inositol metabolism and content, phosphatidylinositol levels, and Na+/K+ pump activity were restored or completely returned to normal values. These functions were also significantly improved, except for the phosphatidylinositol content, which was increased by 55%, when galactose-conditioned cells were incubated for 24 hours in unsupplemented medium. The polyol content of the glucose- or galactose-conditioned cells was also significantly reduced. Returning the cells to normal glucose levels for 1 to 3 hours did not completely restore myo-inositol metabolism. Improved myo-inositol metabolism and content, sorbitol levels, and Na+/K+ ATPase transport activity were also obtained within 24 hours when cells chronically exposed to medium supplemented with 30 mmol/L glucose were placed in medium containing 30 mmol/L glucose and 0.4 mmol/L sorbinil. The phosphatidylinositol content of these cells was improved by approximately 30%. Cells prelabeled for 24 hours with [U-14C]sorbitol metabolize more than 50% of the [U-14C]sorbitol during a 24-hour incubation in unsupplemented medium. These studies conducted at the cellular level suggest that restoration of normal myo-inositol metabolism, polyol content, and Na+/K+ pump activity altered by hyperglycemic conditions occurs rapidly following normalization of glucose concentration.
 ...
PMID:Reversal of hyperglycemic-induced defects in myo-inositol metabolism and Na+/K+ pump activity in cultured neuroblastoma cells by normalizing glucose levels. 841 73

beta-D-Xylosides are often used to competitively inhibit proteoglycan synthesis by serving as primers for free glycosaminoglycan (GAG) chain assembly. Quite unexpectedly, we found that when human melanoma cells and Chinese hamster ovary cells are labeled with [3H] galactose in the presence of 4-methyl umbelliferyl beta-D-xyloside (Xyl beta 4MU), a large portion of the labeled acceptor does not consist of the expected GAG chains, but of the novel GM3 ganglioside-like structure: Sia-alpha 2,3-[3H]Gal beta 1, 4Xyl beta 4MU. Moreover, formation of this derivative is associated with an inhibition of glycosphingolipid synthesis by up to 78% without affecting synthesis of other [3H]Gal-labeled glycoconjugates. Inhibition occurs rapidly and equally for all glycolipid species and is partially abrogated by brefeldin A. Inhibition requires the addition of a single galactose residue to the xyloside within the lumen of the Golgi apparatus. This addition appears to be carried out by galactosyl transferase I that normally synthesizes the core region of GAG chains. Although alpha-xyloside does not inhibit proteoglycan synthesis, it is galactosylated, but not sialylated, and is nearly as effective as a beta-xyloside at inhibiting glycolipid biosynthesis. Similar results were obtained for human macrophage U937, and differentiated or undifferentiated PC12 cells. However, in neuroblastoma cell line MR23, no low molecular weight xyloside products were made and glycolipid synthesis was not inhibited. These results suggest that some of the previously documented effects of beta-xylosides might result, in part, from their inhibition of glycolipid synthesis. The mechanism of inhibition is not a direct competition for glycolipid synthesizing enzymes; rather, it is an unexplained result of formation of Gal beta 1,4Xyl-1 (alpha or beta)4MU.
 ...
PMID:Alpha- and beta-xylosides alter glycolipid synthesis in human melanoma and Chinese hamster ovary cells. 842 Sep 36

Neuroblastoma cells were used to examine the effect of chronic exposure to increased concentrations of glucose, galactose, or L-fucose on bradykinin-stimulated intracellular calcium release using the calcium indicator fluo-3. Bradykinin caused a concentration dependent increase in the intracellular calcium concentration and phosphoinositide hydrolysis in neuroblastoma cells. Norepinephrine, carbachol, serotonin, and thapsigargin also increased the calcium concentration. Treatment of the cells with 10(-6) M bradykinin exhausts calcium release such that the successive treatment of the cells with norepinephrine, carbachol, or serotonin results in no secondary response. In contrast, bradykinin treatment of the cells following exposure to norepinephrine, carbachol, or serotonin caused a secondary increase in calcium release. These results suggest that several hormone responsive calcium pools may exist in neuroblastoma cells or that norepinephrine, carbachol, or serotonin may not fully stimulate calcium release. Bradykinin-stimulated calcium release is not effected by chronic exposure of the cells to increased concentrations of glucose, galactose, or L-fucose. Suggesting that hormone-stimulated calcium release is not an abnormality that develops in neural cells exposed to conditions that mimic the diabetic milieu. In addition, these studies provide evidence that fluo-3 is a good fluorescent indicator for the study of calcium mobilization in cultured neuroblastoma cells.
 ...
PMID:Effect of bradykinin on cytosolic calcium in neuroblastoma cells using the fluorescent indicator fluo-3. 849 91

The metabolism and metabolic effects of succinic acid methyl esters were examined in both NG108-15 mouse neuroblastoma x rat glioma hybrid cells and normal rat brain cells. The conversion of the dimethyl ester of 14C-labeled succinic acid (10 mM) to 14CO2 only represented 5% or less of that found at an equimolar concentration of D-[U- 14C]glucose. Neither the monomethyl nor the dimethyl ester of succinic acid exerted any significant effect upon the metabolism of D-glucose. Likewise, D-glucose (10 mM) failed to significantly affect the oxidation of the dimethyl ester of either [1,4- 14C]succinic acid or [2,3- 14C]succinic acid. It is concluded that, at variance with the situation recently documented in rat pancreatic islets and hepatocytes, the methyl esters of succinic acid are poorly metabolized in neural cells.
 ...
PMID:Metabolism of succinic acid methyl esters in neural cells. 858 55

Defective tissue perfusion and nitric oxide production and altered myo-inositol metabolism and protein kinase C activation have been invoked in the pathogenesis of diabetic complications including neuropathy. The precise cellular compartmentalization and mechanistic interrelationships of these abnormalities remain obscure, and nitric oxide possesses both neurotransmitter and vasodilator activity. Therefore the effects of ambient glucose and myo-inositol on nitric oxide-dependent cGMP production and protein kinase C activity were studied in SH-SY5Y human neuroblastoma cells, a cell culture model for peripheral cholinergic neurons. D-Glucose lowered cellular myo-inositol content, phosphatidylinositol synthesis, and phosphorylation of an endogenous protein kinase C substrate, and specifically reduced nitric oxide-dependent cGMP production a time- and dose-dependent manner with an apparent IC50 of approximately 30 mM. The near maximal decrease in cGMP induced by 50 mM D-glucose was corrected by the addition of protein kinase C agonists or 500 microM myo-inositol to the culture medium, and was reproduced by protein kinase C inhibition or downregulation, or by myo-inositol deficient medium. Sodium nitroprusside increased cGMP in a dose-dependent fashion, with low concentrations (1 microM) counteracting the effects of 50 mM D-glucose or protein kinase C inhibition. The demonstration that elevated D-glucose diminishes basal nitric oxide-dependent cGMP production by myo-inositol depletion and protein kinase C inhibition in peripheral cholinergic neurons provides a potential metabolic basis for impaired nitric oxide production, nerve blood flow, and nerve impulse conduction in diabetes.
 ...
PMID:Modulation of basal nitric oxide-dependent cyclic-GMP production by ambient glucose, myo-inositol, and protein kinase C in SH-SY5Y human neuroblastoma cells. 860 30

Gangliosides of the plasma membrane are important modulators of cellular functions. Previous work from our laboratory had suggested that a plasma membrane sialidase was involved in growth control and differentiation in cultured human neuroblastoma cells (SK-N-MC), but its substrates had remained obscure. We now performed sialidase specificity studies in subcellular fractions and found ganglioside GM3 desialylating activity in presence of Triton X-100 to be associated with the plasma membrane, but absent in lysosomes. This Triton-activated plasma membrane enzyme desialylated also gangliosides GD1a, GD1b, and GT1b, thereby forming GM1; cleavage of GM1 and GM2, however, was not observed. Sialidase activity towards the glycoprotein fetuin with modified C-7 sialic acids and towards 4-methylumbelliferyl neuraminate was solely found in lysosomal, but not in plasma membrane fractions. The role of the plasma membrane sialidase in gangliosides desialylation of living cells was examined by following the fate of [3H]galactose-labelled individual gangliosides in pulse-chase experiments in absence and presence of the extracellular sialidase inhibitor 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. When the plasma membrane sialidase was inhibited, radioactivity of all gangliosides chased at the same rate. In the absence of inhibitor, GM3, GD1a, GD1b, GD2, GD3 and GT1b were degraded at a considerably faster rate in confluent cultures, whereas the GM1-pool seemed to be filled by the desialylation of higher gangliosides. The results thus suggest that the plasma membrane sialidase causes selective ganglioside desialylation, and that such surface glycolipid modification triggers growth control and differentiation in human neuroblastoma cells.
 ...
PMID:Selective ganglioside desialylation in the plasma membrane of human neuroblastoma cells. 872 44

The short-term (less than 2 min) alterations in the intracellular free calcium concentration in differentiated NG108-15 (neuroblastoma cross glioma) cells exposed to dynamic mechanical deformation with and without superimposed chemical hypoxia were determined. A previously developed device, modified for these studies, was used to apply deformations at a magnitude and rate representative of those experienced by neural tissue in Traumatic Brain Injury. Chemical hypoxia was imposed using a combination of 2-deoxy-D-glucose and salicylate, anaerobic and aerobic metabolic blockers, respectively. Real time measurement of intracellular free calcium concentration using Fura-2 and a custom epifluorescence microscopy system provided a quantitative index of cell response. At high rates of deformation (approximately 10 sec-1), increases in intracellular free calcium concentration were exponentially related to the magnitude of the applied deformation. Chemical hypoxia had no effect on this acute response. At low rates of deformation, small increases in intracellular free calcium concentration were independent of the magnitude of the deformation. These findings indicate that strategies for reducing severity of TBI should focus on minimizing the rate of deformation of neural cells. Together with data from animal, physical, and finite element models, these data can be employed in the development of physiologic injury tolerance criteria for the whole head.
 ...
PMID:Acute alterations in [Ca2+]i in NG108-15 cells subjected to high strain rate deformation and chemical hypoxia: an in vitro model for neural trauma. 886 95

Al-trans retinoic acid (RA) enhanced human, S-type, SK-N-SH neuroblastoma cell invasion of reconstituted basement membrane in vitro but did not induce terminal differentiation of this cell line. In contrast to basal invasion, which was urokinase (uPA)- and plasmin-dependent, RA-enhanced invasion was dependent on tissue-type plasminogen activator (t-PA) and plasmin activity. Neither basal nor RA-enhanced invasion involved TIMP-2 inhibitable metalloproteinases. Enhanced invasion was associated with the induction of t-PA expression, increased expression of the putative t-PA receptor amphoterin, increased association of t-PA with cell membranes and increased net membrane-associated PA activity. Enhanced invasion was not associated with significant changes in the expression of uPA or its membrane receptor UPAR; plasminogen activator inhibitors PAI-1 and PAI-2; metalloproteinases MMP-1, MMP-2, MMP-3, MMP-9 and membrane type MMP1; or tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2. RA stimulated the association of t-PA with the external cell membrane surface, which could be inhibited by heparin sulphate but not by mannose sugars or chelators of divalent cations, consistent with a role for amphoterin. Our data indicate that RA can promote the malignant behavior of S-type neuroblastoma cells refractory to RA-mediated terminal differentiation by enhancing their basement membrane invasive capacity. We suggest that this results from the action of a novel, RA-regulated mechanism involving stimulation of t-PA expression and its association with the cell membrane leading to increased PA-dependent matrix degradation.
 ...
PMID:Retinoic acid-enhanced invasion through reconstituted basement membrane by human SK-N-SH neuroblastoma cells involves membrane-associated tissue-type plasminogen activator. 939 56

Large-volume leukapheresis (LVL), defined as the processing of at least three blood volumes in a single session for peripheral blood progenitor cell (PBPC) collection, was performed in 32 small children weighing < or = 25 kg, aged 10 months to 8 years, with a variety of malignancies. Harvesting of PBPC was started after 4 days of cytokine (G-CSF, 12 micrograms/kg s.c.) alone. Procedures were performed using a continuous flow blood cell separator (COBE Spectra). The automated program of lymphocytapheresis was modified to achieve a collection rate of 0.9 ml/min. The extracorporeal line was primed with a unit of a packed red blood cells before the procedure. Acid citrate dextrose (ACD) was used as anticoagulant with an ACD inlet ratio of 1:14 and an ACD infusion rate of 1.1 ml/min/L of total blood volume. The inlet flow ranged between 6 and 35 ml/min (median 20 ml/min). A total of 37 apheresis procedures were performed (median 1, range 1-3). In 84% of patients, a single apheresis yields the minimum number of PBPC cells required for transplantation. No consistent side effects were observed, and LVL was well tolerated by children. A median of 7.7 x 10(8) kg MNC, 5.4 x 10(6)/kg CD34+, and 6.2 x 10(4)/kg CFU-GM per apheresis were harvested. Patients with neuroblastoma had a significantly lower yield than other patients. To date, 27 patients have been transplanted after myeloablative treatment, and rapid and sustained engraftment was achieved in all cases. The number of CD34+ cells infused was highly correlated with engraftment kinetics. LVL can be safely and easily performed in small children, allowing adequate PBPC collection for transplantation with rapid hematologic recovery.
 ...
PMID:Peripheral blood progenitor cell collection by large-volume leukapheresis in low-weight children. 950 82


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