Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Na,K-ATPase, which catalyzes the active transport of Na(+) and K(+), has two principal subunits (alpha and beta) that have several genetically distinct isoforms. Most of these isoforms are expressed in the nervous system, but certain ones are preferentially expressed in glia and others in neurons. Of the beta isoforms, beta1 predominates in neurons and beta2 in astrocytes, although there are some exceptions. Here we demonstrate that beta3 is expressed in rat and mouse white matter oligodendrocytes. Immunofluorescence microscopy identified beta3 in oligodendrocytes of rat brain white matter in typical linear arrays of cell bodies between fascicles of axons. The intensity of stain peaked at 20 postnatal days. beta3 was identified in cortical oligodendrocytes grown in culture, where it was expressed in processes and colocalized with antibody to galactocerebroside. In the mouse and rat optic nerve, beta3 stain was seen in oligodendrocytes, where it colocalized with carbonic anhydrase II. For comparison, optic nerve was stained for the beta1 and beta2 subunits, showing distinct patterns of labelling of axons (beta1) and astrocytes (beta2). The C6 glioma cell line was also found to express the beta3 isoform preferentially. Since beta3 was not found at detectable levels in astrocytes, this suggests that C6 is closer to oligodendrocytes than astrocytes in the glial cell lineage.
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PMID:Oligodendrocytes in brain and optic nerve express the beta3 subunit isoform of Na,K-ATPase. 1094 Nov 47

The accumulation levels of 201TlCl and Na(+)-K+ ATPase activity in tumor tissue were compared among glioblastoma, benign glioma and meningioma to study the difference in the mechanism of 201TlCl accumulation. The subjects were 19 cases comprised of 6 glioblastoma, 2 oligodendroglioma, 1 fibrillary astrocytoma, 1 pilocytic astrocytoma and 9 meningioma. Preoperative 201TlCl SPECT was performed in all the cases, and Thallium Index (TL index) was calculated by a ratio of 201TlCl in the tumor area and the contralateral area. In addition, cell membrane was extracted from the tumor tissue collected intraoperatively to determine Na(+)-K+ ATPase activity. No statistically significant difference in TL index was noted between the glioblastoma group (6.97 +/- 2.67) and the meningioma group (5.87 +/- 1.99). This fact showed that there was no difference in the accumulation level of 201TlCl between the two groups. On the other hand, the glioblastoma group indicated a higher value of Na(+)-K+ ATPase activity (49.13 +/- 43.76 mumole/hour/mg protein) than the meningioma group (7.73 +/- 13.84 mumole/hour/mg protein) (p < 0.05, t test). These results suggested the involvement of Na(+)-K+ ATPase activity in 201TlCl accumulation in glioblastoma and the influences of other accumulation mechanism than Na(+)-K+ ATPase activity such as the volume of intratumoral vascular bed in meningioma.
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PMID:[Difference in 201TlCl accumulation mechanism in brain tumors: a comparison of their Na(+)-K+ ATPase activities]. 1096 51

Previous work from this laboratory had demonstrated the presence of endogenous morphine, strychnine and nicotine in the mammalian brain and human serum samples. Morphine is synthesised from tyrosine and strychnine and nicotine from tryptophan. This study examines the role of strychnine, nicotine and morphine in neuropsychiatric disorders. The blood levels of tyrosine, tryptophan, strychnine, nicotine and morphine were studied as also RBC membrane Na(+)-K+ ATPase activity. It was found that serum tyrosine levels were reduced and tryptophan levels elevated in all neuropsychiatric disorders studied with a reduction in RBC Na(+)-K+ ATPase activity. Nicotine was present in significant amounts in serum of patients with schizophrenia, CNS glioma and syndrome X with multiple lacunar state. Morphine was present in significant amounts only in the serum of patients with multiple sclerosis and MDP. Strychnine was present in significant amounts in the serum of patients with epilepsy, Parkinson's disease and MDP. The presence of nicotine and strychnine in significant amounts could be related to elevated tryptophan levels suggesting the synthesis of these alkaloids from tryptophan. Morphine was not detected in most of the disorders owing to low tyrosine levels noted in them. Na(+)-K+ ATPase inhibition noticed in most of the disorders could be related to decreased hyperpolarising morphinergic transmission and increased depolarising nicotinergic and strychinergic transmission. The role of morphine, strychnine and nicotine in the pathogenesis of these disorders in the setting of membrane Na(+)-K+ ATPase inhibition is discussed.
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PMID:Endogenous strychnine, nicotine, and morphine--description of hypo and hyper-strychninergic, nicotinergic and morphinergic state in relation to neuropsychiatric diseases. 1111 26

Two substances which are products of the isoprenoid pathway, can participate in lipid peroxidation. One is digoxin, which by inhibiting membrane Na(+)-K+ ATPase, causes increase in intracellular Ca2+ and depletion of intracellular Mg2+, both effects contributing to increase in lipid peroxidation. Ubiquinone, another products of the pathway is a powerful membrane antioxidant and its deficiency can also result in defective electron transport and generation of reactive oxygen species. In view of this and also in the light of some preliminary reports on alteration in lipid peroxidation in neuropsychiatric disorders, a study was undertaken on the following aspects in some of these disorders (primary generalised epilepsy, schizophrenia, multiple sclerosis, Parkinson's disease and CNS glioma)--1) concentration of digoxin, ubiquinone, activity of HMG CoA reductase and RBC membrane Na(+)-K+ ATPase 2) activity of enzymes involved in free radical scavenging 3) parameters of lipid peroxidation and 4) antioxidant status. The result obtained indicates an increase in the concentration of digoxin and activity of HMG CoA reductase, decrease in ubiquinone levels and in the activity of membrane Na(+)-K+ ATPase. There is increased lipid peroxidation as evidenced from the increase in the concentration of MDA, conjugated dienes, hydroperoxides and NO with decreased antioxidant protection as indicated by decrease in ubiquinone, vit E and reduced glutathione in schizophrenia, Parkinson's disease and CNS glioma. The activity of enzymes involved in free radical scavenging like SOD, catalase, glutathione peroxidase and glutathione reductase is decreased in the above diseases. However, there is no evidence of any increase in lipid peroxidation in epilepsy or MS. The role of increased operation of the isoprenoid pathway as evidenced by alteration in the concentration of digoxin and ubiquinone in the generation of free radicals and protection against them in these disorders is discussed.
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PMID:Isoprenoid pathway and free radical generation and damage in neuropsychiatric disorders. 1127 6

The effects of chemotherapy [25 mg/kg 1,3-bis(2-chloroethyl)-1-nitrosourea administered with a single i.p. injection] on cellular energetics by 31P nuclear magnetic resonance (NMR) spectroscopy, total tissue sodium by single-quantum (SQ) 23Na NMR spectroscopy, and intracellular sodium by triple-quantum-filtered (TQF) 23Na NMR spectroscopy were studied in the s.c. 9L glioma. Animals were studied by NMR 2 days before therapy and 1 and 5 days after therapy. Destructive chemical analysis was also performed 5 days after therapy to validate the origin of changes in SQ and TQF 23Na signals. One day after treatment, there was no significant difference between control and treated tumors in terms of tumor size or 23Na and 31P spectral data. Five days after therapy, treated tumors had 28 +/- 16% (P < 0.1) lower SQ 23Na signal intensity, 46 +/- 20% (P < 0.05) lower TQF 23Na signal intensity, 125 +/- 51% (P < 0.05) higher ATP:Pi ratio, 186 +/- 69% (P < 0.05) higher phosphocreatine:Pi ratio, and 0.17 +/- 0.06 pH units (P < 0.05) higher intracellular pH compared with control tumors. No significant differences in TQF 23Na relaxation times were seen between control and treated tumors at any time point. Destructive chemical analysis showed that the relative extracellular space of control and treated tumors was identical, but the treated tumors had 21 +/- 8% (P < 0.05) lower total tissue Na+ concentration and 60 +/- 24% (P < 0.05) lower intracellular Na+ concentration compared with the controls. The higher phosphocreatine:Pi and ATP:Pi ratios after 1,3-bis(2-chloroethyl)-1-nitrosourea treatment indicate improved bioenergetic status in the surviving tumor cells. The decrease in SQ and multiple-quantum-filtered 23Na signal intensity was largely attributable to a decrease in Na(i)+ because the treatment did not change the relative extracellular space. The improved energy metabolism could decrease the intracellular concentration of Na+ by increasing the activity of Na+-K+-ATPase and decreasing the activity of Na+/H+. Although both 23Na and 31P spectra were consistent with improved cellular metabolism in treated tumors, the 23Na methods may be better suited for monitoring response to therapy because of higher signal:noise ratio and ease of imaging the single 23Na resonance.
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PMID:Effects of chemotherapy by 1,3-bis(2-chloroethyl)-1-nitrosourea on single-quantum- and triple-quantum-filtered 23Na and 31P nuclear magnetic resonance of the subcutaneously implanted 9L glioma. 1128 Jul 59

Vacuolar H(+) ATPase (V-ATPase) activity is essential for many cellular processes, including intracellular membrane traffic, protein processing and degradation, and receptor-mediated endocytosis. Proton transport by V-ATPases could also play a role during cell transformation, tumorigenesis, and cell metastasis, and V-ATPase c-subunit overexpression was reported to be correlated with invasiveness of pancreatic tumors (Ohta et al., 1996). In the present work, we found that mRNAs encoding V-ATPase subunits are not overexpressed in C6 tumoral glioma cells when compared with immortalized astrocytes DI TNC1 and astrocytes in primary cultures. Accordingly, V-ATPase subunit mRNA levels are similar in human gliomas (grade II or IV) and in peritumoral tissues. A significant proportion (25%) of V-ATPase is present in the plasma membrane of both the C6 and the DI TNC1 astrocytic cells in culture. A bafilomycin-sensitive hyperpolarizing pump current through the plasma membrane was detected and measured after ionic channel inhibition, which corresponds most probably to an electrogenic transport of protons. This suggests that the plasma membrane V-ATPase is active. It could contribute to cytoplasmic pH regulation in astrocytic cells.
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PMID:Functional expression of V-ATPases in the plasma membrane of glial cells. 1187 Aug 75

The purpose of this study was to investigate the relationship among ultrastructural angiogenic features, adenosine-5'-triphosphatase (ATP-ase) activities and superoxide dismutase (SOD) concentration in the microvasculature of intracranial meningiomas and glial tumors. We examined 20 tumor materials from 20 adult patients with intracranial meningioma or glial tumor who underwent selective surgery, dividing them into two groups based on the type of the tumors. Group I consisted of 10 meningioma-materials, and Group II of 10 glial tumor-materials. Na+-K+, Mg+2 and Ca+2 ATP-ase activities in Group I were significantly higher than those in Group II (p < 0.01). The SOD activity in Group I was significantly lower than that in Group II (p < 0.01). According to electron microscopic findings, vascular endothelial proliferation and ultrastructural cytoplasmic changes in the glial tumors were more prominent than those in the meningiomas. Our results show that there is a meaningful correlation among an increased endothelial proliferation, a decreased ATP-ase level and an increased SOD activity in the meningiomas and glial tumors.
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PMID:The relationships among ultrastructural angiogenic features, Na+ K+, Ca+2, Mg+2 ATP-ase activities and SOD concentration in the microvasculature of intracranial meningiomas and glial tumors. 1195 23

It has recently been suggested that an increase in brain-derived neurotrophic factor (BDNF) expression may mediate some of the therapeutic effect of antidepressant drugs, via their effects on the neurotransmitter 5-hydroxytryptamine (5-HT). However, because it is unclear whether 5-HT manipulations directly affect BDNF expression, we examined BDNF mRNA levels in C6 glioma cells following incubation with 5-HT using reverse transcription polymerase chain reaction (RT-PCR) and Northern blot analysis. Incubation of C6 glioma cells with 5-HT increased the BDNF mRNA expression approx twofold. The effect of 5-HT (100 microM) was inhibited by a 5-HT2A receptor antagonist (ketanserin; 1 microM). The RNA synthesis inhibitor (actinomycin D; 10 microg/mL), but not a protein synthesis inhibitor (cycloheximide; 0.5 microg/mL) blocked the effect of 5-HT. Furthermore, incubation of C6 glioma cells with EGTA (1 mM), a protein kinase inhibitor (staurosporine; 1 microM), the Ca2+ ATPase inhibitor thapsigargin (1 microM), or a calcium/calmodulin-dependent kinase inhibitor (KN 62; 1 microM) inhibited the response to 5-HT. Our data show that 5-HT increases de novo BDNF mRNA synthesis following direct activation of the 5-HT2A receptor, via a calcium-dependent and protein kinase-dependent pathway.
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PMID:5-HT2A receptor activation leads to increased BDNF mRNA expression in C6 glioma cells. 1209 61

Alteration in the isoprenoid metabolites--digoxin, ubiquinone, and dolichol--have been reported in neuronal degeneration (Parkinson's disease), oncogenesis (central nervous system glioma), functional neuropsychiatric disorders (schizophrenia and epilepsy), and immune-mediated disorders (multiple sclerosis). The coexistence of these disorders has been documented in literature and a central dysfunction related to digoxin and the isoprenoid pathway may underlie all these disorders. A family with a high prevalence of Parkinson's disease, schizophrenia, neoplasms, syndrome X, rheumatoid arthritis, and epilepsy has been described. The psychological behavioral patterns of the family were: creativity and high IQ, hypersexual behavior, reduced appetite and eating behavior, insomnia and reduced sleep patterns, increased tendency for spirituality, increased tendency for addiction, less bonding and affectionate behavior, and left handedness/right hemispheric dominance. Digoxin, an endogenous Na(+)-K+ ATPase inhibitor secreted by the hypothalamus, was found to be elevated and red blood cell (RBC) membrane Na(+)-K+ ATPase activity was found to be reduced in all the disorders and in the indexed family studied. Hypothalamic digoxin can modulate conscious perception and its dysfunction may lead to schizophrenia. Digoxin can also preferentially upregulate tryptophan transport over tyrosine, resulting in increased levels of depolarizng tryptophan catabolites, serotonin, quinolinic acid, strychnine, and nicotine, and decreased levels of hyperpolarizing tyrosine catabolites, dopamine, noradrenaline, and morphine, contributing to membrane Na(+)-K+ ATPase inhibition in all the above disorders and the indexed family. Digoxin-induced membrane Na(+)-K+ ATPase inhibition can result in increased intracellular Ca2+ and reduced Mg2+ levels, leading on to glutamate excitotoxicity, oncogene activation, and immune activation. Digoxin-induced altered Ca2+/Mg2+ ratios, reduced ubiquinone, and increased dolichol can affect glycoconjugate metabolism, membrane formation and structure, and mitochondrial function, leading to the diverse disorders described above, including those in the indexed family. The isoprenoid pathway and neurotransmitter patterns were compared in right-handed/LH dominant and left-handed/RH dominant individuals. The left-handed/RH dominant individuals compared to right-handed/LH dominant individuals had elevated hydroxymethylglutarylcoenzyme A reductase activity, with increased serum digoxin and dolichol levels. The serum ubiquinone, serum Mg2+ and RBC Na(+)-K+ ATPase activity were reduced in left-handed/RH dominant individuals. The left-handed/RH dominant individuals compared to right-handed/LH dominant individuals had elevated levels of serum tryptophan, quinolinic acid, serotonin, nicotine, and strychnine. The levels of tyrosine, dopamine, noradrenaline, and morphine were low in left-handed/RH dominant compared to right-handed/LH dominant individuals. The hyperdigoxinemic state indicates right hemispheric dominance. Hypothalamic digoxin can thus function as the master conductor of the neuroimmunoendocrine orchestra and coordinate the functions of various cellular organelles.
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PMID:Central role of hypothalamic digoxin in conscious perception, neuroimmunoendocrine integration, and coordination of cellular function: relation to hemispheric dominance. 1232 12

The blood-brain barrier (BBB) was modelled in this study using ECV304 cells in co-culture with rat C6 glioma cells, which resulted in elevated transendothelial electrical resistance (TEER). The inflammatory mediator bradykinin (1 microM) was studied and found to induce a fall in TEER; the link between this change and intracellular free calcium concentration ([Ca(2+)](i)) was then examined. 1 microM bradykinin produced a peak-plateau increase in [Ca(2+)](i). The peak showed desensitization and was dose dependent (over 0.1 nM to 1 microM). The [Ca(2+)](i) increase was blocked by the B(2) antagonist HOE 140 (1 microM) without effect from a B(1) agonist and antagonist. The plateau response was abolished in Ca(2+)-free solution containing 2 mM EDTA, and also by the Ca(2+) channel blockers lanthanum, La(3+) (10 microM), and SKF 96365 (100 microM). The store Ca(2+)ATPase inhibitor thapsigargin (1 microM) abolished the peak response. The putative phospholipase C inhibitors, U73122 (20 microM) and ETH-18-OCH(3) (100 microM), unexpectedly increased [Ca(2+)](i); after their application, bradykinin was ineffective. Agents without effect on Ca(2+) responses to bradykinin included the phospholipase A(2) (PLA(2)) inhibitor aristolochic acid (0.5 mM), cyclooxygenase inhibitor indomethacin (100 microM), 5-lipoxygenase inhibitor nordihydroguaiaretic acid, NDGA (100 microM), calphostin C (0.5 microM), L-NAME (1 mM) and nifedipine (10 microM). The fall in TEER from bradykinin was blocked by HOE 140, U73122 and thapsigargin combined with La(3+), and also by aristolochic acid and NDGA, but not indomethacin, calphostin C or L-NAME. U73122 increased TEER while ETH-18-OCH(3) reduced it. Thus bradykinin reduced TEER through B(2) receptor-linked release of Ca(2+) from thapsigargin-sensitive stores, leading to activation of PLA(2) and metabolism of arachidonic acid by 5-lipoxygenase.
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PMID:Bradykinin increases permeability by calcium and 5-lipoxygenase in the ECV304/C6 cell culture model of the blood-brain barrier. 1238 49


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