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

S-100 protein in clonal GA-1 and C6 rat glioma cell lines was released in serum-free medium supplemented with adrenocorticotropic hormone (ACTH). The induction of S-100 protein release by ACTH was dose-dependent, showing a half-maximal release at about 5 microM, and the S-100 protein concentration in the medium increased sharply within 3 min, but slightly during further incubation. The S-100 protein release was apparently accompanied by a decrease in the membrane-bound form of S-100 protein in the cell. The S-100 protein release was induced not by the ACTH1-24 fragment, which exhibits the known effects of ACTH, but by the ACTH18-39 fragment, which is designated as corticotropin-like intermediate-lobe peptide (CLIP). These results indicate that the C-terminal half of ACTH is responsible for the S-100 protein release. The enhancement of S-100 protein release by ACTH was also observed in normal rat glioblasts. The release induced by ACTH was apparently specific to S-100 protein, because little release of the cytoplasmic enzymes, creatine kinase, and enolase was observed under the same conditions. High concentrations (5 mM) of dibutyryl cyclic AMP or dibutyryl cyclic GMP were also found to induce S-100 protein release; however, catecholamines (epinephrine, norepinephrine, isoproterenol, and dopamine), acetylcholine, and glutamic acid did not enhance the release.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:S-100 protein in clonal astroglioma cells is released by adrenocorticotropic hormone and corticotropin-like intermediate-lobe peptide. 282 56

For the determination of their possible utility as tumors markers, 2 neural-associated isozymes, neuron-specific enolase [(NSE) EC 4.2.1.11] and creatine kinase BB [(CK-BB) EC 2.7.3.2], were quantitated by radioimmunoassay in human neuroectodermal-derived cell lines, primary brain tumors, and sera and cerebrospinal fluid (CSF) from brain tumor patients. The NSE content of neuroblastoma cell lines was more than sixfold that of the glioma and medulloblastoma lines; the CK-BB content of neuroblastoma and medulloblastoma lines was fourfold to nineteen-fold that of the glioma and other lines. Expression of NSE in neuroblastoma cell lines was not related to time in culture and was cell line specific. NSE in ex vivo medulloblastomas was raised six to ten times that in astrocytomas and gliomas, although no significant differences were noted for the CK-BB content. Serum and CSF NSE levels were markedly raised above control values in 10 of 29 and 6 of 10 cases of astrocytoma, respectively. Raised CK-BB levels in serum (greater than 10 ng/ml) and CSF (greater than 12 ng/ml) were found in 9 of 18 and 2 of 10 patients, respectively. These data suggest that NSE is preferentially expressed by neuroblastoma lines and medulloblastomas and that NSE and CK-BB may have clinical utility as markers for prognosis, diagnosis, and monitoring of response to therapy.
 ...
PMID:Differential expression of neural isozymes by human medulloblastomas and gliomas and neuroectodermal cell lines. 346 6

We have recently shown that while brain creatine kinase (CKB) mRNA was detectable in RNA from cultured primary rat brain neurons, CKB mRNA was about 15-fold higher in primary astrocytes and 17-fold higher in oligodendrocytes (Molloy et al., J Neurochem 59:1925-1932, 1992). To begin to understand the molecular mechanisms responsible for brain glial cells containing the highest levels of CKB mRNA in the body, we have examined the expression of rat CKB mRNA in established C6 glioma cells. RNase-protection analysis showed the endogenous CKB mRNA levels in exponentially growing C6 were high and measured 50% of that in total RNA from rat brain lysate and 60% of that in cultured primary astrocytes and oligodendrocytes. The 5' and 3' ends of CKB mRNA in C6 were mapped to the same nucleotides as CKB mRNA from rat brain, indicating that the sites of in vivo transcription initiation and termination/polyadenylation of CKB mRNA in C6 are the same as in total rat brain RNA. The level of CKB enzyme activity in C6 whole cell lysates was among the highest of the glial cell lines which we measured. All creatine kinase enzyme activity present in C6 was found in the dimeric CKB isoform (BB), which is characteristic of CKB expression in the brain. A 2.9 kb gene fragment containing the basal CKB promoter and far-upstream 5' sequences was cloned upstream of the chloramphenicol acetyltransferase (CAT) gene and transfected into C6 cells. CAT activity was readily detectable in C6 and mapping of the 5' end of the CAT mRNA showed that transcription was directed from the correct initiation site. Since we found C6 cells were difficult to transfect, conditions were established which both maximized transfection efficiency and maintained normal C6 cell morphology. These results should permit the future identification of the nuclear trans-acting factors and the cognate cis-acting regulatory elements responsible for high CKB mRNA expression in brain glial cells.
 ...
PMID:Expression of the rat brain creatine kinase gene in C6 glioma cells. 851 Jan 86

Cyclocreatine (CY), an analogue of creatine, inhibits tumor growth in vivo and proliferation of tumor cells in vitro. The goal of this study was to probe the mechanism of CY transport and cytotoxicity in C6 rat glioma cells and OC238 human ovarian carcinoma cells (creatine kinase activities of 0.16 and 0.016 units/mg protein, respectively). In both cell lines, CY significantly inhibited cell growth with no effect on membrane integrity and on the content of nucleoside triphosphates. An intrinsic 31P-nuclear magnetic resonance (31P-NMR) signal of phosphocreatine, as well as accumulation of phosphocyclocreatine (PCY) after addition of CY, was observed for C6 glioma but not for the OC238 cells. Transport of CY in C6 glioma showed Michaelis-Menten kinetics for an active sodium-dependent component. Transport was reduced more than fivefold in low-glucose medium. The toxicity of CY to C6 glioma cells may be due to PCY accumulation and cellular swelling. Another mechanism must be invoked to explain CY effects on the human ovarian cancer cells in which no PCY accumulation could be detected and no cellular swelling was observed.
 ...
PMID:Cyclocreatine transport and cytotoxicity in rat glioma and human ovarian carcinoma cells: 31P-NMR spectroscopy. 877 41

The cytoplasmic creatine kinase (CKB) enzyme has a central role in the regeneration of ATP in the brain. We have shown previously that CKB mRNA levels in cultured primary rat brain astrocytes and oligodendrocytes are much higher than in primary neurons. It has been suggested that high CKB expression is essential for the energy-demanding functions of glial cells. Conversely, CKB may be repressed in most neuronal cells; however, CKB protein has previously been detected by immunohistochemistry in several distinct groups of neurons in the adult rodent brain. Presently, little is known of the factors responsible for the high CKB expression in glia and possible repression in neurons. In this report, we investigated if low CKB mRNA was characteristic of some established neuronal cell lines. CKB mRNA was found to be extremely low in mouse C1300 neuroblastomas NS20Y and N1E-115 but 10-fold higher in NG108-15, a hybrid cell composed of a C1300 neuroblastoma and a rat C6 glioma. Since we showed NG108-15 contained only rat CKB mRNA transcribed from the C6 glioma CKB gene, expression of CKB mRNA may be a manifestation of a glial property in NG108-15 cells. However, CKB mRNA expression in NG108-15 appeared not to be fully activated since it was still 5-fold lower than in (parental) C6 glioma and 10-fold lower than in cellular RNA from either total rat brain or cultured primary astrocytes. When neuronal differentiation was increased in NS20Y and N1E-115 by treating cells with prostaglandin E1 and theophylline, the extremely low CKB mRNA level was not significantly changed. In a comparative study, the CKB mRNA levels in NS20Y, N1E-115 and neuronal RT4-B8 and RT4-E5 cells (from the rat RT4 peripheral neurotumor) were at least 50-fold lower than that in C6 glioma and 100-fold lower than in cultured primary astrocytes. These cell lines may provide a system for the identification of factors involved in the possible repression of CKB in many neuronal cells.
 ...
PMID:Expression of the brain creatine kinase gene is low in neuroblastoma cell lines. 932 58

3-Hydroxyglutaric acid (3HGA) accumulates in the inherited neurometabolic disorder known as glutaryl-CoA dehydrogenase deficiency. The disease is clinically characterized by severe neurological symptoms, frontotemporal atrophy and striatum degeneration. Because of the pathophysiology of the brain damage in glutaryl-CoA dehydrogenase deficiency is not completed clear, we investigated the in vitro effect of 3HGA (0.01-5.0mM) on critical enzyme activities of energy metabolism, including the respiratory chain complexes I-V, creatine kinase isoforms and Na(+),K(+)-ATPase in cerebral cortex and striatum from 30-day-old rats. Complex II activity was also studied in rat C6-glioma cells exposed to 3HGA. The effect of 3HGA was further investigated on the rate of oxygen consumption in mitochondria from rat cerebrum. We observed that 1.0mM 3HGA significantly inhibited complex II in cerebral cortex and C6 cells but not the other activities of the respiratory chain complexes. Creatine kinase isoforms and Na(+),K(+)-ATPase were also not affected by the acid. Furthermore, no inhibition of complex II activity occurred when mitochondrial preparations from cerebral cortex or striatum homogenates were used. In addition, 3HGA significantly lowered the respiratory control ratio in the presence of glutamate/malate and succinate under stressful conditions or when mitochondria were permeabilized with digitonin. Since 3HGA stimulated oxygen consumption in state IV and compromised ATP formation, it can be presumed that this organic acid might act as an endogenous uncoupler of mitochondria respiration. Finally, we observed that 3HGA changed C6 cell morphology from a round flat to a spindle-differentiated shape, but did not alter cell viability neither induced apoptosis. The data provide evidence that 3HGA provokes a moderate impairment of brain energy metabolism and do not support the view that 3HGA-induced energy failure would solely explain the characteristic brain degeneration observed in glutaryl-CoA dehydrogenase deficiency patients.
 ...
PMID:3-Hydroxyglutaric acid moderately impairs energy metabolism in brain of young rats. 1611 21

Accumulation of the branched-chain alpha-keto acids (BCKA), alpha-ketoisocaproic acid (KIC), alpha-keto-beta-methylvaleric acid (KMV), and alpha-ketoisovaleric acid (KIV) and their respective branched-chain alpha-amino acids (BCAA) in tissues and biological fluids is the biochemical hallmark of patients affected by the neurometabolic disorder known as maple syrup urine disease (MSUD). Considering that brain energy metabolism is possibly altered in MSUD, the objective of this study was to determine creatine kinase (CK) activity, a key enzyme of energy homeostasis, in C6 glioma cells exposed to BCKA. The cells were incubated with 1, 5, or 10 mM BCKA for 3 h and the CK activity measured afterwards. The results indicated that the BCKA significantly inhibited CK activity at all tested concentrations. Furthermore, the inhibition caused by the BCKA on CK activity was totally prevented by preincubation with the energetic substrate creatine and by coincubation with the N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, indicating that deficit of energy and nitric oxide (NO) are involved in these effects. In contrast, other antioxidants such as glutathione (GSH) and trolox (soluble Vitamin E) were not able to prevent CK inhibition. In addition, we observed that the C6 cells changed their usual rounded morphology when exposed for 3 h to 10 mM BCKA and that creatine and L-NAME prevented these morphological alterations. Considering the importance of CK for brain metabolism homeostasis, it is conceivable that inhibition of this enzyme by increased levels of BCKA may contribute to the neurodegeneration of MSUD patients.
 ...
PMID:Creatine and antioxidant treatment prevent the inhibition of creatine kinase activity and the morphological alterations of C6 glioma cells induced by the branched-chain alpha-keto acids accumulating in maple syrup urine disease. 1663 2

Gliomas in the form of astrocytomas, anaplastic astrocytomas and glioblastomas are the most common brain tumors in humans. Early detection of these cancers is crucial for successful treatment. Proteomics promises the discovery of biomarkers and tumor markers for early detection and diagnosis. In the current study, a differential gel electrophoresis technology coupled with matrix-assisted laser desorption/ionization-time of flight and liquid chromatography-tandem mass spectroscopy was used to investigate tumor-specific changes in the proteome of human brain cancer. Fifty human brain tissues comprising varying diagnostic groups (non-tumor, grade I, grade II, grade III and grade IV) were run in duplicate together with an internal pool sample on each gel. The proteins of interest were automatically picked, in-gel digested and mass spectrometry fingerprinted. Two hundred and eleven protein spots were identified successfully and were collapsed into 91 unique proteins. Approximately 20 of those 91 unique proteins had, to our knowledge, not been reported previously as differentially expressed in human brain cancer. Alb protein, peroxiredoxin 4 and SH3 domain-binding glutamic acid-rich-like protein 3 were upregulated in glioblastoma multiform versus non-tumor tissues. However, aldolase C fructose-biphosphate, creatine kinase, B chain dihydrolipoyl dehydrogenase, enolase 2, fumarate hydratase, HSP60, lactoylglutathione lyase, lucine aminopeptidase, Mu-crystallin homolog, NADH-UO 24, neurofilament triplet L protein, septin 2, stathmin and vacuolar ATP synthase subunit E were downregulated in glioblastoma multiform compared with non-tumor tissues. These differentially expressed proteins provided novel information on the differences existing between normal brain and gliomas, and thus might prove to be useful molecular indicators of diagnostic or prognostic value.
 ...
PMID:Biomarker discovery: a proteomic approach for brain cancer profiling. 1723 37

Many naturally occurring substances of plant origin ingested in human diet, exhibit anticarcinogenic and antimutagenic effects. One of the active phytochemical which shows the active anticarcinogenic role is Piper longum Linn. (Pl). Pl is widely used in ayurvedic industry due to its property in healing some of the bodily ailments. Despite being known for the antioxidant, antimicrobial and anticarcinogenic effects, its relation to brain and its tumour development is still scarce. Hence, the experimental glioma model was developed in rats using C6 glioma cells and the effect of Pl was evaluated in the brain tissue of experimental group of rats. From the study, the glioma induced animals showed an increased level of lipid peroxides (LPO), tissue marker enzymes lactate dehydrogenase (LDH), creatine kinase (CK), 5'nucleotidase (5'ND) and acetylcholine esterase (AChE). But Pl treatment (20 mg/kg body weight) significantly attenuated these alterations thereby showing potent anticancer effect in glioma induced rats. In addition, the anticarcinogenic effect of Pl was confirmed by microscopic analysis and the restoration of increased lipids and protein bound carbohydrates (PBCs) in the brain tissue of glioma induced rats. Hence our results implicate a major role for Pl in preventing the cancer development in the experimental glioma model.
 ...
PMID:Studies on the neuroprotective role of Piper longum in C6 glioma induced rats. 1973 Jul 92

Methylmercury (MeHg), a potent neurotoxicant, easily passes through the blood-brain barrier and accumulates in brain causing severe irreversible damage. However, the underlying neurotoxic mechanisms elicited by MeHg are still not completed defined. In this study, we aimed to investigate the in vitro toxic effects elicited by crescent concentrations (0-1500 microM) of MeHg on creatine kinase (CK) activity, thiol content (NPSH) and protein carbonyl content (PCC) in mouse brain preparations. In addition, CK activity, MTT reduction and DCFH-DA oxidation (reactive oxygen species (ROS) formation) were also measured in C6 glioma cell linage. CK activity was severely reduced by MeHg treatment in mouse brain preparations. This inhibitory effect was positively correlated to the MeHg-induced reduction of NPSH levels and increment in PCC. Moreover, the positive correlation between brain CK activity and NPSH levels was observed at either 15 or 60 min of MeHg pre-incubation. In addition, MeHg-treated C6 cells showed also a significant inhibition of CK activity at MeHg concentrations, as low as, 50 microM in parallel to reduced mitochondrial function and increased ROS production. Taking together, these data demonstrate that MeHg severely affects CK activity, an essential enzyme for brain energy buffering to maintain cellular energy homeostasis. This effect appears to be mediated by oxidation of thiol groups that might cause subsequent oxidative stress.
 ...
PMID:Oxidative stress-mediated inhibition of brain creatine kinase activity by methylmercury. 2056 54


1