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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of mRNAs encoding hexokinase isozymes was studied in various cells such as rat brain, liver, skeletal muscle, kidney and heart, and the rat hepatoma cell line AH130 by Northern blotting. High specific expression of type II hexokinase was observed only with AH130 cells. In contrast, specific expression of type I hexokinase was detected in energy-requiring normal tissue cells such as brain and heart. These results suggest that the expression of hexokinase isozyme in the tumor cells is different from that in normal cells.
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PMID:Remarkably enhanced expression of the type II hexokinase in rat hepatoma cell line AH130. 193 51

We recently proposed that extracellular ATP (ATPo) may be involved in CTL-mediated cytotoxicity by acting in concert with yet unidentified cellular components (ATPo receptors/ATPo-binding proteins, ectoprotein kinases). The TCR-triggered ATPo accumulation by CTL has been demonstrated, whereas the resistance of CTL to ATPo was explained by the action of highly active ecto-ATPases or by the absence of relevant ATP-binding proteins. However, no data were available to discriminate between the possibilities of: i) ATPo acting alone as a "hit" molecule because of the cell-permeabilizing properties of ATP4- or ii) ATPo acting as a "messenger" (as MgATP2-) in concert with other molecules. Comparing ATPo-induced and CTL-mediated cell lysis, we found that ATPo-induced lysis of some target cells is greatly decreased at neutral and acidic pH, whereas Ca(2+)-dependent CTL-mediated lysis of the same cells is barely affected. In agreement with the observed pH dependency, at low Mg2+ concentrations, which favor ATP4- over MgATP2-, maximal ATPo-induced lysis was observed. However, CTL-mediated cytotoxicity in both Ag-specific and retargeting assays was markedly reduced at low Mg2+ concentrations. These results suggest that ATPo acting alone as a "hit" molecule cannot fully account for the extracellular Ca(2+)-dependent lethal hit delivery by CTL or that ATP4- is active at very low concentrations. This conclusion was further supported by studying the lytic effect of ATPo and CTL on the anti-TCR mAb-coupled SRBC. CTL were efficient in the SRBC lysis, whereas no lysis of SRBC by ATPo was detected. The resistance of SRBC to ATPo is not caused by a high ATPo degradation, because the ecto-ATPase activity of SRBC was much lower than in ATPo-resistant CTL OE4 cells and comparable with EL4 tumor cells, which were easily lysed by ATPo. These data suggested the need for careful consideration of the pH and cation composition of the media used for studying ATPo effects. The caveats in the use of ATP-degrading enzymes to implicate the role of extracellular ATPo in the CTL-mediated cytotoxicity are described here. A clarification of the previously described cytotoxicity inhibition by hexokinase, which is caused by an inhibitory salt effect, is presented. It is suggested that if Ca(2+)-dependent lysis of SRBC and of other target cells by CTL does involve extracellular ATP, it may function as a "messenger" in concert with other extracellular molecules.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparative studies of the cytotoxic T lymphocyte-mediated cytotoxicity and of extracellular ATP-induced cell lysis. Different requirements in extracellular Mg2+ and pH. 194 Mar 62

Rats bearing the Walker-256 carcinosarcoma have a profoundly altered liver metabolite content with significant increases in the concentrations of glucose 6-phosphate, fructose 1,6-bisphosphate, citrate, lactate, and alanine, while the concentrations of glucose, pyruvate, dihydroxyacetone phosphate, and glutamine are decreased. As a result of these changes both the cytosolic NAD+/NADH ratio and the cytosolic phosphorylation potential are significantly lowered while no changes are detected in either the cytosolic NADP+/NADPH ratio or the mitochondrial NAD+/NADH ratio. These hepatic changes are accompanied by marked increases in the circulating concentrations of lactate, non-esterified fatty acids, and triacylglycerols. The activities of both liver hexokinase and phosphofructokinase are also significantly elevated in the tumor-bearing rats. The changes observed both in the redox state and phosphorylation potential are in agreement with the energy imbalance associated with tumor burden.
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PMID:The energy state of tumor-bearing rats. 199 70

Hexokinase is a key enzyme in carbohydrate metabolism. Its activity has been shown elevated in cells with high mitotic index. In particular, experimental cancer cells, due to their peculiar energy metabolism, display a hexokinase activity proportional to the degree of malignancy. This is the case also for human gliomas in which glucose metabolism, evaluated via positron emission tomography, has been shown to be predictive for patient prognosis. In order to better correlate these findings, specific reagents for tumor hexokinase (a polyclonal antibody and a full-length cDNA probe both specific for murine tumor hexokinase) have been successfully employed to quantitate the protein and its messenger in cultured cell lines; the antibody was also tested in four specimens obtained from human astrocytomas.
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PMID:The membrane-bound hexokinase as a potential marker for malignancy in human gliomas. 209 98

The alterations in specific activity and/or isozyme pattern of hexokinase, phosphofructokinase, aldolase, enolase, pyruvate kinase and glucose-6-phosphate dehydrogenase were studied in the tissue specimens of 26 patients with lipoblastic tumors and 28 patients with tumors of neurogenic origin. Although the biochemical data demonstrated that the activities of most enzymes studied were elevated in the specimens of the malignant tumors, only the differences in activity of hexokinase, pyruvate kinase and glucose-6-phosphate dehydrogenase measured between benign and malignant neurogenic tumors were significant. In malignant tumors, especially those of neurogenic origin, the isozyme pattern of pyruvate kinase showed a shift towards K-type subunits.
Tumour Biol 1990
PMID:Activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase in lipoblastic and neurogenic proliferations. 216 88

The combination of phorbol 12-myristate 13-acetate (PMA) and concanavalin A induces the expression of a new set of glycolytic isozymes in human peripheral lymphocytes. The induced isozyme for each enzyme tested (hexokinase, phosphofructokinase, enolase, pyruvate kinase and lactate dehydrogenase) is usually the muscle form, which is often associated with rapidly dividing tumor cells. Increases in a specific isozyme can account for the 2-5-fold increase in specific activities of the enzyme induced by Con A plus PMA. Increased specific activities and the appearance of the new isozyme forms both occur relatively late, and are probably associated with the G1 or S phase of the cell cycle.
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PMID:Expression of a new set of glycolytic isozymes in activated human peripheral lymphocytes. 216 15

Some biochemical characteristics of rat sarcoma M-1 transplanted into skeletal muscle have been investigated. Data on the key enzyme activity of the carbohydrate metabolism on the different stages of neoplasia are reported. The isozyme content and intracellular location of hexokinase in sarcoma M-1 have been studied specially.
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PMID:[The characteristics of sarcoma M-1 in rats]. 220 14

A major energy source in brain is glucose, which is committed to metabolism by hexokinase (Type I isozyme), an enzyme usually considered to be bound to the outer mitochondrial membrane. In this study, the subcellular location of hexokinase in brain has been rigorously investigated. Mitochondrial fractions containing hexokinase (greater than 500 milliunits/mg protein) were prepared by two different procedures, and then subjected to density gradient centrifugation before and after loading with barium phosphate, a technique designed to increase the density of the mitochondria. The gradient distribution patterns of both unloaded and loaded preparations show that brain hexokinase does not distribute exclusively with mitochondrial marker enzymes. This is particularly evident in the loaded preparations where there is a clear distinction between the peak activities of hexokinase and mitochondrial markers. The same observation was made when the mitochondrial fraction of either untreated or barium phosphate-loaded mitochondria was subjected to titration with digitonin. In fact, at concentrations of digitonin, which almost completely solubilize marker enzymes for both the inner and outer mitochondrial membranes, a significant fraction of the total hexokinase remains particulate bound. Electron microscopy confirmed that particulate material is still present under these conditions. Significantly, hexokinase is released from particulate material only at high concentrations of digitonin which solubilize the associated microsomal marker NADPH-cytochrome c reductase. Glucose 6-phosphate, which is known to release hexokinase from the brain "mitochondrial fraction" also releases hexokinase from this unidentified particulate component. These results on brain, a normal glucose utilizing tissue, differ from those obtained previously on highly glycolytic tumor cells where identical subfractionation procedures revealed a strictly outer mitochondrial membrane location for particulate hexokinase (Parry, D. M., and Pedersen, P. L. (1983) J. Biol. Chem. 258, 10904-10912). It is concluded that in brain, hexokinase has a greater propensity to localize at nonmitochondrial receptor sites than to those known to be associated with the outer mitochondrial membrane.
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PMID:Glucose catabolism in brain. Intracellular localization of hexokinase. 229 99

In rapidly growing tumor cells exhibiting high glucose catabolic rates, the enzyme hexokinase is markedly elevated and bound in large amounts (50-80% of the total cell activity) to the outer mitochondrial membrane (Arora, K.K., and Pedersen, P.L. (1988) J. Biol. Chem. 263, 17422-17428; Parry, D.M., and Pedersen, P.L. (1983) J. Biol. Chem. 258, 10904-10912). In extending these studies, we have isolated a cDNA clone of hexokinase from a lambda gt11 library of the highly glycolytic, c37 mouse hepatoma cell line. This clone, comprising 4,198 base pairs, contains a single open reading frame of 2,754 nucleotides which encode a 918-amino acid hexokinase with a mass of 102,272 daltons. This enzyme exhibits, respectively, 68 and 32 amino acid differences, including several charge differences, from the recently sequenced human kidney and rat brain enzymes. The putative glucose and ATP binding domains present in the latter two enzymes and in rat liver glucokinase are conserved in the tumor enzyme. At its N-terminal region, tumor hexokinase has a 12-amino acid hydrophobic stretch which is present in the rat brain enzyme but absent in the rat liver glucokinase, a cytoplasmic enzyme. The mature tumor hexokinase protein has been overexpressed in active form in Escherichia coli and purified 9-fold. The overexpressed enzyme binds to rat liver mitochondria in the presence of MgCl2. This is the first report describing the cloning and sequencing of a tumor hexokinase, and the first report documenting the overexpression of any hexokinase type in E. coli. Questions pertinent to the enzyme's mechanism, regulation, binding to mitochondria, and its marked elevation in tumor cells can now be addressed.
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PMID:Glucose phosphorylation in tumor cells. Cloning, sequencing, and overexpression in active form of a full-length cDNA encoding a mitochondrial bindable form of hexokinase. 231 62

The specific activity of hexokinase, phosphofructokinase, aldolase, enolase, pyruvate kinase and glucose-6-phosphate dehydrogenase was measured in 41 smooth muscle cell tumors: 20 leiomyomas and 21 cases of leiomyosarcoma. Statistical analysis revealed no significant differences in specific activity between normal smooth muscle tissue and the benign and malignant tumors originating from it. Quantification of the isozyme composition of pyruvate kinase showed a significant shift in isozyme pattern towards K-type subunits in leiomyosarcomas as compared to leiomyomas.
Tumour Biol 1990
PMID:Activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase in smooth muscle proliferation. 237 98


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