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)

Nine monoclonal antibodies directed against DPP IV from rat liver plasma membranes were obtained. They recognized four different epitopes (A, B, C and D) of the enzyme. The epitopes A, B and C were located on the outside of the hepatocyte plasma membrane and were shared by DPP IV from hepatoma plasma membrane and the soluble form. Epitope D appeared to be partly inserted in the membrane and was found exclusively in the liver. Epitopes A, B and C and DPP IV revealed by histochemical means showed similar distribution patterns on frozen sections of various rat tissues, while epitope D did not show such a correlation. DPP IV is inserted in liver plasma membrane by two different mechanisms, one being phospholipase C-sensitive, while in hepatoma the enzyme is anchored in this membrane by a phospholipase C-resistant mechanism only.
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PMID:Characterization of different forms of dipeptidyl peptidase IV from rat liver and hepatoma by monoclonal antibodies. 290 14

A major glycoprotein of rat hepatoma plasma membranes was selectively released as a soluble form by incubating the membrane with phosphatidylinositol-specific phospholipase C. The soluble form corresponding to the glycoprotein was also prepared by butan-1-ol extraction of microsomal membranes at pH 5.5, whereas extraction at pH 8.5 yielded an electrophoretically different form with a hydrophobic nature. The soluble glycoprotein extracted at pH 5.5 was purified by sequential chromatography on concanavalin A-Sepharose, Sephacryl S-300 and anti-(alkaline phosphatase) IgG-Sepharose, the last step being used to remove a contaminating alkaline phosphatase. The glycoprotein thus purified was a single protein with Mr 130,000 in SDS/polyacrylamide-gel electrophoresis, although it behaved as a dimer in gel filtration on Sephacryl S-300. The glycoprotein was analysed for amino acid and carbohydrate composition. The composition of the carbohydrate moiety, which amounted to 64% by weight, suggested that the glycoprotein contained much larger numbers of N-linked oligosaccharide chains than those with O-linkage. It was confirmed that the purified glycoprotein was immunologically identical not only with that released by the phospholipase C but also with the hydrophobic form extracted with butan-1-ol at pH 8.5. The results indicate that the glycoprotein of rat hepatoma plasma membranes, which has an unusually high content of carbohydrate, is another membrane protein released by phosphatidylinositol-specific phospholipase C, as documented for alkaline phosphatase, acetylcholinesterase and Thy-1 antigen.
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PMID:Purification and characterization of a major glycoprotein in rat hepatoma plasma membranes. One of the membrane proteins released by phosphatidylinositol-specific phospholipase C. 303 62

A glycophospholipid has been purified from rat liver membranes, which copurified with an insulin-sensitive glycophospholipid isolated from H35 hepatoma cells. The polar head group of this glycophospholipid, which is a phosphooligosaccharide, was generated by treatment with a phosphatidylinositol-specific phospholipase C from Staphylococcus aureus. There was an "insulin-like" inhibitory effect of this phosphooligosaccharide on isoproterenol-stimulated lipolysis in adipocytes, whereas there was no effect on glucose oxidation under conditions that measure glucose transport. The antilipolytic effect of this phosphooligosaccharide was demonstrated in intact adipocytes. There was a linear correlation between the concentration of phosphooligosaccharide and its antilipolytic effect, the magnitude and time course of which were similar to that obtained with physiological concentrations of insulin. Submaximal concentrations of insulin and phosphooligosaccharide produced an additive antilipolytic effect. The antilipolytic effect of the phosphooligosaccharide was demonstrated only after release of this compound from the precursor glycophospholipid with phosphatidylinositol-specific phospholipase C, and the activity of the phosphooligosaccharide was sensitive to alkali. It is proposed that this phosphooligosaccharide plays a role in mediating certain insulin actions.
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PMID:Glucose transport and antilipolysis are differentially regulated by the polar head group of an insulin-sensitive glycophospholipid. 330 76

A glycophospholipid has been purified from rat liver membranes and shown to copurify with an insulin-sensitive glycophospholipid isolated from H35 hepatoma cells. The polar head group of this glycophospholipid is a phospho-oligosaccharide generated by treatment with phosphatidylinositol-specific phospholipase C from Staphylococcus aureus. It has been proposed that this phospho-oligosaccharide, which is also generated in response to insulin, may play a role in insulin action. Incubation of the catalytic subunit of cyclic AMP-dependent protein kinase with this phospho-oligosaccharide inhibited the activity of the kinase to phosphorylate histone IIA, a purified preparation of phospholipid methyltransferase and kemptide, a phosphate-accepting peptide. Inhibition of kinase activity was dose-dependent and 50% inhibition of histone phosphorylation was demonstrated with a concentration of phospho-oligosaccharide of around 2 microM. This effect was demonstrated in the presence of ATP at concentrations up to 1 mM, indicating that the phospho-oligosaccharide acts at physiological concentrations of ATP and that it does not compete with this nucleotide for the same binding site in the kinase. Inhibition by the phospho-oligosaccharide of kinase activity could be reversed by dilution or dialysis and was not reproduced by up to 50 microM myo-inositol, glucosamine, galactose, myo-inositol 1-phosphate, glucosamine 1-phosphate, galactose 1-phosphate or phosphorylcholine. The inhibitory activity was resistant to mild acid treatment but was labile to treatment with alkali, exposure to nitrous acid or incubation with sodium periodate. The phospho-oligosaccharide had no effect on the phosphorylation of lysine-rich histone by rat brain protein kinase C and on the binding of cyclic AMP to a cyclic AMP-dependent protein kinase. In conclusion, the data in this study suggested that a phospho-oligosaccharide generated from an insulin-sensitive glycophospholipid may play a role in insulin action by modulating cyclic AMP-dependent protein kinase activity.
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PMID:Inhibition of cyclic AMP-dependent protein kinase by the polar head group of an insulin-sensitive glycophospholipid. 333 45

The effects of tumour-promoting phorbol esters on the receptor-mediated endocytosis of insulin were investigated in the human hepatoma cell line HepG2. Treatment of these cells with the biologically active phorbol 12-O-tetradecanoylphorbol 13-acetate (TPA), but not with the non-tumour-promoting analogue 4 alpha-phorbol 12,13-didecanoate, resulted in dramatic morphological changes, which were accompanied by a 1.5-2.5-fold increase in specific 125I-insulin association with the cells at 37 degrees C. This increase in insulin binding was not observed when the binding reaction was performed at 4 degrees C. The potentiation of 125I-insulin association with TPA-treated cells at 37 degrees C could be completely accounted for by an increase in the intracellular pool of internalized insulin; there was no concomitant increase in cell-surface insulin binding. Dissociation studies showed that the enhanced internalization of insulin by cells after treatment with TPA resulted from a decrease in the rate of intracellular processing of the insulin after receptor-mediated endocytosis. The phorbol-ester-induced enhancement of internalized insulin in HepG2 cells was additive with the potentiation of endocytosed insulin induced by both the lysosomotropic reagent chloroquine and the ionophore monensin; this indicates that TPA affects the intracellular processing of the insulin receptor at a point other than those disrupted by either of these two reagents. The potentiation of insulin receptor internalization by tumour-promoting phorbol esters could be completely mimicked by treatment with phospholipase C, but not with phospholipase A, and partially mimicked by treatment with the synthetic diacylglycerol 1-oleoyl-2-acetylglycerol. By these criteria, the effects of phorbol esters on the insulin receptor in HepG2 cells appear to be mediated through protein kinase C. These results support the concept that the activation of protein kinase C by treatment with phorbol esters causes a perturbation of the insulin-receptor-mediated endocytotic pathway in HepG2 cells, reflected in a long-term decreased rate of dissociation of internalized insulin by the phorbol-ester-treated cells.
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PMID:Potentiation of specific association of insulin with HepG2 cells by phorbol esters. 353 1

A phospholipid has been purified from rat liver membranes which copurified with an insulin-sensitive glycophospholipid isolated from H35 hepatoma cells. The polar head group of this phospholipid was generated by treatment with a phosphatidylinositol-specific phospholipase C from Staphylococcus aureus and purified through a C18 extraction column. Like insulin, the addition of this polar head group to isolated rat adipocytes inhibited the stimulatory effect of isoproterenol on phospholipid methyltransferase. The polar head group was also active on a subcellular fraction. The addition of the polar head group to microsomes isolated from isoproterenol-treated adipocytes produced a time-dependent inactivation of phospholipid methyltransferase, approaching basal activity. It is proposed that the effects of insulin on phospholipid methyltransferase may be mediated by this polar head group.
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PMID:The polar head group of a novel insulin-sensitive glycophospholipid mimics insulin action on phospholipid methyltransferase. 353 37

This study identifies and partially characterizes an insulin-sensitive glycophospholipid in H35 hepatoma cells. The incorporation of [3H]glucosamine into cell lipids was investigated. A major labeled lipid was purified by sequential thin layer chromatography using first an acid followed by a basic solvent system. After hydrochloric acid hydrolysis and sugar analysis by thin layer chromatography, 80% of the radioactivity in the purified lipid was found to comigrate with glucosamine. H35 cells were prelabeled with [3H]glucosamine for either 4 or 24 h and treated with insulin causing a dose-dependent stimulation of turnover of the glycophospholipid which was detected within 1 min. The purified glycolipid was cleaved by nitrous acid deamination indicating that the glucosamine C-1 was linked to the lipid moiety through a glycosidic bond. [14C]Ethanolamine, [3H]inositol, and [3H]sorbitol were not incorporated into the purified glycolipid. The incorporation of various fatty acids into this glycolipid was also studied. [3H]Palmitate was found to be preferentially incorporated while myristic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, and arachidonic acid were either not incorporated or incorporated less than 10% of palmitate. The purified glycolipid labeled with [3H]palmitate was cleaved by treatment with phospholipase A2 but was resistant to mild alkali hydrolysis suggesting the presence of a 1-hexadecyl,2-palmitoyl-glyceryl moiety in the purified lipid. Treatment of labeled glycophospholipid with phosphatidylinositol-specific phospholipase C from Staphylococcus aureus generated a compound migrating as 1-alkyl,2-acyl-glycerol and a polar head group with a size in the range from 800 to 3500. These findings coupled with the nitrous acid deamination demonstrate that glucosamine was covalently linked through a phosphodiester bond to the glyceryl moiety of the purified glycolipid. These findings suggest that insulin acts on this glycophospholipid by stimulating an insulin-sensitive phospholipase C. This unique glycophospholipid may play an important role in insulin action by serving as precursor of insulin-generated mediators.
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PMID:Identification of a novel insulin-sensitive glycophospholipid from H35 hepatoma cells. 354 86

The enzyme GDPFuc:GM1 alpha 1----2 fucosyltransferase, induced by chemical carcinogens in precancerous rat liver as well as rat hepatoma cells, was found previously to be membrane bound, and was inactivated by various detergents, while the activities of many other transferases are generally enhanced by detergents (Holmes, E.H. & Hakomori, S. (1983) J. Biol. Chem. 258, 3706-3717). The effects of phospholipids and detergents on rat hepatoma H35 cells, the conditions of solubilization and subsequent affinity chromatography of the enzyme, and a possible association of phospholipids with the enzyme have been studied with the following major results: The alpha 1----2 fucosyltransferase activity in Golgi membrane was diminished on treatment of membranes with phospholipase A1 or phospholipase C. The enzyme activity was stimulated 7-fold in the presence of cardiolipin or phosphatidylglycerol (and 3-fold by phosphatidylethanolamine) but not other phospholipids. The stimulatory effect of phosphatidylglycerol was eliminated when a variety of ionic or non-ionic detergents were added to the reaction mixture, with the exception of the cationic detergent G-3634-A, which provided a 10-fold total stimulation in the presence of phosphatidylglycerol. The kinetic analysis indicated that addition of phosphatidylglycerol has a negligible effect on apparent Km values but increases the Vmax of the enzyme 5- to 6-fold. The enzyme activity was solubilized by the dialyzable detergent CHAPSO without inhibition of the enzyme activity, and the solubilized enzyme in the presence of 0.4% CHAPSO is partially purified by chromatography on GDP-hexanolamine-Sepharose. Removal of CHAPSO from the affinity purified enzyme by dialysis resulted in a 66% loss of the original activity, which was restored by addition of phosphatidylglycerol. Chromatography of the affinity-purified enzyme with 3H-labeled phosphatidylglycerol on a Biogel A0.5 column indicated an association of the enzyme with the phospholipid that occurred only in the absence of detergent. These results suggest that phospholipid has a direct effect on the enzyme and that the inhibitory effect of detergents can be ascribable to disturbing interaction between phospholipids and the enzyme. A possible role of specific phospholipids on in vivo transferase activity for glycolipids is discussed.
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PMID:The chemical carcinogen-induced enzyme, GDP-fucose: GM1 alpha 1----2 fucosyltransferase in rat liver and hepatoma: modulation by and association with phospholipids. 365 87

The lipid dependence of pyrophosphatase activity was studied by treatment of liver and hepatoma microsomes with phospholipase C from Cl. perfringens and B. cereus and a subsequent incorporation of various classes of phospholipids into the delipidated microsomes. Phospholipase C hydrolysis sharply lowers the pyrophosphatase activity of liver and hepatoma microsomes. The enzyme activity is restored after introduction of phospholipids into delipidated liver microsomes, the maximal effect being achieved on incorporation of phosphatidylcholine. All the phospholipids tested exerted the same reactivation effects on the delipidated microsomes of hepatoma. However, a more complete delipidation of hepatoma microsomes by phospholipase C hydrolysis and a subsequent organic solvent extraction revealed a specific dependence of the enzyme activity on phosphatidylserine.
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PMID:[Investigation of the lipid dependence of pyrophosphatase activity from rat liver microsomes and hepatoma by phospholipase C]. 612 25

A phosphooligosaccharide has been proposed as a second messenger of insulin. It is believed to be structurally related to the carbohydrate moiety of phosphatidylinositol glycan anchors of many cell surface proteins. Herein we demonstrate that [32]phosphate in freshly isolated adipocytes and [3H]galactose in cultured hepatoma cells (H4IIE) labeled the same set of three different glycolipids. With all three, the radiolabel was made water soluble by phosphatidylinositol(glycan)-specific phospholipase C or D catalyzed hydrolysis. We isolated the three phospholipase C-released substances. One of them was susceptible to nitrous acid deamination, indicative of a hexosamine with a free amino group. This phosphooligosaccharide structure had an apparent molecular mass between tetra- and pentaglucose by gel filtration. By anion-exchange chromatography it was separated into two differently charged and interconvertible species. Adipocytes stimulated with insulin accumulated the nitrous acid sensitive phosphooligosaccharide: after stimulation the intracellular level of free phosphooligosaccharide increased threefold within 5 min, fell off during the next few minutes and then remained at a slightly elevated level. After insulin stimulation the intracellular concentration of free phosphooligosaccharide was > 1,000-fold higher than in the incubation medium. When prepared from rat livers on a preparative scale, the oligosaccharide was also found to exhibit insulinomimetic effects on protein phosphorylation of insulin target proteins in intact adipocytes. After subcellular fractionation of adipocytes the lipid-bound [32P]phosphooligosaccharide of the plasma membrane was found to be localized in plasma membrane domains apparently corresponding to caveolae. Lipid-bound [32P]phosphooligosaccharide was found also in the microsomal fraction.
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PMID:Isolation of phosphooligosaccharide/phosphoinositol glycan from caveolae and cytosol of insulin-stimulated cells. 755 70


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