Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibody raised against the human erythrocyte glucose transporter identified a recombinant lambda gt11 bacteriophage in a cDNA library prepared from immunoselected polysomal RNA from adult rat brain. The cDNA predicts a 492-amino acid protein that demonstrates 97.6% identity to the human hepatoma hexose carrier. The tissue distribution of the transporter mRNA is identical to that of immunologically identifiable protein and transport activity, except in liver in which high levels of transport are associated with little or no transporter mRNA or protein. As assayed by blot-hybridization analysis, mRNA from insulin-responsive and nonresponsive tissues are indistinguishable. These data suggest that a genetically unrelated protein is responsible for hexose transport in normal liver.
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PMID:Cloning and characterization of a cDNA encoding the rat brain glucose-transporter protein. 301 20

On polyacrylamide gradient gel electrophoresis, normal serum cholinesterase was separated into seven isozymes (I-VII from the anodic to the cathodic side). The enzyme of the conditioned medium of the HuH-7 cell line, established from a human hepatoma, had two main isozymes. The one migrating faster was located slightly to the cathodic side of band II of the normal serum enzyme, and the other, a slower one, electrophoresed at the same position as that of band VI of the normal serum enzyme. Aside from these two isozymes, a faint band with enzyme activity sometimes appeared at a position just cathodic or very close to the position of band I of the normal serum isozymes. The effect of some inhibitors and activators on both the normal serum enzyme and the enzyme of the conditioned medium was similar, but lectin-binding properties of the two enzymes were different with Ricinus communis agglutinin I, concanavalin A and wheat germ agglutinin. These results suggest that the difference in sugar moieties of both enzymes is expressed in D-galactose, D-mannose and N-acetylglucosamine.
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PMID:Novel cholinesterase expression in the HuH-7 cell line. 303 81

T4-binding globulin (TBG), the principal carrier of thyroid hormone in serum, is a glycoprotein containing 20% carbohydrate. The importance of the carbohydrate moiety has been previously studied by enzymatic deglycosylation, which showed that deglycosylated TBG retains its original immunological an T4-binding properties. However, the structure and properties of TBG before glycosylation and the steps involved in carbohydrate addition have not been explored. In the present report, we used a human hepatoma cell line (Hep G2) which synthesizes and secretes TBG into the medium. This TBG binds T4 and possesses immunoreactivity and microheterogeneity identical to those of native TBG (nTBG) from serum. Cells were pulsed with [35S]methionine, [3H]mannose, and [3H]glucosamine in the absence or presence of 5 micrograms tunicamycin/ml medium. Materials from cells and media were immunoprecipitated with antibodies specific for nTBG and denatured TBG molecule. They were then analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cells incubated with [35S]methionine contained two forms of labeled TBG, with apparent mol wt of 60K (TBG1) and 54K (TBG2). Medium contained only the TBG1 form, which is identical to nTBG in serum. In contrast, in the presence of tunicamycin, the predominant intracellular form of TBG had an apparent mol wt of 44K (TBG3). At no time was this material detected in the medium. [3H]Mannose and [3H]glucosamine labeled both TBG1 and TBG2, but not TBG3. TBG1 and TBG2 reacted with anti-nTBG serum, whereas TBG3 reacted only with anti-dentured TBG serum, specific for the unfolded TBG molecule. Intracellular TBG was rich (80-90%) in high mannose (seven to nine mannose residues) oligosaccharides and was relatively poor (10-20%) in complex-type species, resistant to endoglycosidase H. These results indicate that 1) the precursor nonglycosylated 44K TBG3 is glycosylated to produce TBG2 (54K) and TBG1 (60K); 2) TBG2 contains oligosaccharides rich in mannose and appears to be a major intracellular intermediate in the synthesis of TBG1; 3) only the endoglycosidase H-resistant TBG1 is secreted; and 4) prior glycosylation of TBG appears to be required for the molecule to assume its tertiary structure and, ultimately, for its secretion. However, once the peptide chain is folded, removal of the carbohydrate moieties does not alter the tertiary structure.
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PMID:The role of glycosylation in the molecular conformation and secretion of thyroxine-binding globulin. 308 30

Two X-linked genes, specifying ornithine transcarbamoylase (OTC) and glucose-6-phosphate dehydrogenase (Glc-6-PD), are reversibly suppressed in certain derivatives of the rat H4-II-E hepatoma. Either gene can become reactivated spontaneously, and it is shown that both can be reactivated by azacytidine treatment. This gene reactivation has been investigated by enzyme assay and by the use of selective growth media ('ornithine-medium' to select for OTC, and medium containing diamide to select for Glc-6-PD). There is a clear tendency for both genes to be reactivated together, though either can become active alone. Since OTC is an enzyme of the urea-cycle, and Glc-6-PD is an enzyme of the hexose monophosphate shunt, and since these two pathways are normally under quite separate control, it would seem that the coupled regulation of the two genes in these hepatomas is abnormal. It is suggested that the suppression of the two genes resembles X-inactivation: in both cases, azacytidine treatment induces gene reactivation with a high frequency and results in different clones of cells expressing widely varying amounts of enzyme activity. The association between the re-expression of OTC and Glc-6-PD might indicate that some phenomenon like the position-effect is occurring.
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PMID:The associated reactivation of two X-linked genes. The spontaneous and azacytidine-induced reexpression of ornithine transcarbamoylase and glucose-6-phosphate dehydrogenase in a rat hepatoma. 608 29

A new cell surface-associated adhesive glycoprotein with a molecular weight of 70,000 was separated from differentiated rat ascites hepatoma cells forming cell islands in vivo (but not from undifferentiated rat ascites hepatoma cells present as single cells in vivo) and highly purified by chromatography; it was synthesized by the cells and localized on the cell surface. Its synthesis began to rise rapidly and reached its peak in 24 hr cultivation, i.e., a 10-fold increase. This substance induced not only aggregation but also adhesiveness of the cells characterized by junctional complexes including tight junctions, desmosomes, and intermediate junctions, closely resembling the frequency and distribution of junctional complexes observed on the above cell islands. Its potency was inhibited specifically by D-mannose and alpha-methyl-D-mannoside; the numbers of the binding sites per cell were calculated as 6 x 10(5). Its activity was concerned with the protein portion of the molecule, and not with the carbohydrate portion. Thus, it seemed reasonable that the adhesive glycoprotein may play a key role in the cell adhesiveness and island formation. In contrast, serum-associated adhesive glycoprotein, separated from normal rat serum, could aggregate the cells but not develop junctional complex.
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PMID:Molecular pathology of cancer cell adhesiveness. 702 74

Rapid kinetic techniques were employed to measure the transport of the nonmetabolizable hexose, 3-O-methyl-D-glucose, in suspensions of human HeLa cells, mouse L- and P388 leukemia cells, and Chinese hamster ovary cells in zero-trans entry and exit and equilibrium exchange procedures. The kinetic parameters of transport were computed by fitting appropriate integrated rate equations to time courses of transmembrane equilibration of radiolabeled substrate. Transport of all four lines, as in Novikoff rat hepatoma cells, conformed to a simple carrier model with directional symmetry but differential mobility of loaded and empty carrier. As was apparent from a comparison of influx and exchange flux, the loaded carrier of all cell types moved between 4 and 14 times faster than the empty carrier. ATP depletion of the cells by incubation in glucose-free medium containing KCN and iodoacetate had no significant effect on the kinetic properties of the transporter. ATP-depleted cells were used to measure the transport of D-glucose, 2-deoxyglucose, D-galactose, and D-glucosamine in the absence of intracellular metabolism. The differential mobilities of empty carrier and carrier loaded with these hexoses and the efficiency of their transport were equivalent to those observed with 3-O-methylglucose, but the Michaelis-Menten constants for the transport of D-galactose and D-glucosamine were 5-8-fold higher than those for D-glucose, 2-deoxy-D-glucose, and 3-O-methylglucose, which were about equivalent.
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PMID:Broad specificity hexose transport system with differential mobility of loaded and empty carrier, but directional symmetry, is common property of mammalian cell lines. 720 77

The kinetics of transport of the non-metabolizable hexose, 3-O-methyl-D-glucose, have been measured in Novikoff rat hepatoma cells by both zero-trans entry and equilibrium exchange procedures. Transport conformed to a simple carrier model which operates symmetrically with respect to direction, but with greater mobility of the loaded than of the empty carrier. Although a complete kinetic description of the transporter can, in theory, be obtained by application of integrated equations describing the time course of substrate equilibrium across the membrane beginning from the zero-trans situation, statistical analysis of hypothetical data indicated that directional asymmetry or differential mobilities of loaded and empty carrier cannot be discerned reliably from such data alone. The difference in mobility of loaded and empty carrier, apparent in a comparison of zero-trans entry and exchange data, ranged from 1.5--7-fold in different batches of cells. It is concluded that the magnitude of the difference is not an inherent property of the transporter, but is determined physiologically, and may be involved in regulation of hexose transport.
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PMID:Hexose transport in Novikoff rat hepatoma cells. A simple carrier with directional symmetry, but variable relative mobilities of loaded and empty carrier. 721 22

The effect of extracellular pH on hexose uptake by cultured Novikoff hepatoma cells has been examined with respect to four distinct parameters: i) the transport of 3-O-methyl-D-glucose, ii) the uptake of 2-deoxy-D-glucose by intact cells, iii) the phosphorylation of 2-deoxy-D-glucose in vitro by cell-free preparations, and iv) the intracellular pH as measured by 5,5'-dimethyl[2-14C]oxazolidine-2,4-dione. Transport per se was not affected by pH in the range of 6 to 8, while uptake of 2-deoxy-D-glucose increased with pH 2- to 3-fold over this range. The pH sensitivity of uptake can be explained on the basis of a change in hexokinase activity effective in situ. The pH dependence of hexokinase observed in vitro, however, was insufficient to account for that apparent in situ.
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PMID:Hexose transport and phosphorylation by Novikoff rat hepatoma cells as function of extracellular pH. 745 78

Mannose-binding protein (MBP) is a plasma protein synthesized by hepatocytes. MBP, a structural analogue of the complement component C1q, can activate complement via the classical pathway and plays an important role in host defence. Expression of the human MBP gene was studied using the human hepatoma cell line HuH-7. RNA extracted from HuH-7 cells was reverse-transcribed to cDNA, amplified by the polymerase chain reaction and analysed by Southern blot hybridization. MBP mRNA expression in HuH-7 cells was increased by interleukin-6 (IL-6), dexamethasone and heat shock, decreased by interleukin 1 (IL-1), and unaffected by interferon gamma (IFN gamma), tumour necrosis factor alpha (TNF alpha) and transforming growth factor beta (TGF beta). Gel shift assays demonstrated Sp-1 binding sites in the 5' region of the gene, and formation of specific complexes between DNA and nuclear protein extracted from HuH-7 cells treated with IL-1 or IL-6. Human MBP is an acute-phase protein, and transcription of its gene is enhanced by IL-6, dexamethasone and heat shock but inhibited by IL-1. The actions of the cytokines appear to be mediated by specific transcription factors.
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PMID:Human mannose-binding protein gene is regulated by interleukins, dexamethasone and heat shock. 825 72

Direct utilization of mannose for glycoprotein biosynthesis has not been studied because cellular mannose is assumed to be derived entirely from glucose. However, animal sera contain sufficient mannose to force uptake through glucose-tolerant, mannose-specific transporters. Under physiological conditions this transport system provides 75% of the mannose for protein glycosylation in human hepatoma cells despite a 50- to 100-fold higher concentration of glucose. This suggests that direct use of mannose is more important than conversion from glucose. Consistent with this finding the liver is low in phosphomannose isomerase activity (fructose-6-P<->mannose-6-P), the key enzyme for supplying glucose-derived mannose to the N-glycosylation pathway. [2-3H] Mannose is rapidly absorbed from the intestine of anesthetized rats and cleared from the blood with a t1/2of 30 min. After a 30 min lag, label is incorporated into plasma glycoproteins, and into glycoproteins of all organs during the first hour. Most (87%) of the initial incorporation occurs in the liver, but this decreases as radiolabeled plasma glycoproteins increase. Radiolabel in glycoproteins also increases 2- to 6-fold in other organs between 1-8 h, especially in lung, skeletal muscle, and heart. These organs may take up hepatic-derived radiolabeled plasma glycoproteins. Significantly, the brain, which is not exposed to plasma glycoproteins, shows essentially no increase in radiolabel. These results suggest that mammals use mannose transporters to deliver mannose from blood to the liver and other organs for glycoprotein biosynthesis. Additionally, contrary to expectations, most of the mannose for glycoprotein biosynthesis in cultured hepatoma cells is derived from mannose, not glucose. Extracellular mannose may also make a significant contribution to glycoprotein biosynthesis in the intact organism.
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PMID:Direct utilization of mannose for mammalian glycoprotein biosynthesis. 945 Oct 38


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